A decade ago Dominic West and Clarke Peters were two working actors living in the same north-west London neighbourhood. At the time they were both making a reasonable if unreliable living on stage and screen, yet they were strangers not just to the general public but also to each other. Then out of the blue they found themselves in the American backwater of Baltimore, starring in The Wire, David Simon's epic portrait of that city's criminal and political classes, and they formed the kind of lasting bond that only the shared participation in a monumental enterprise – like a major war or an exceptional five-season TV series – can provide.

Since The Wire finished filming almost four years ago, several key members of the cast have stayed in touch as some have gone on to enjoy a turbo-charged boost to their careers. Perhaps the most notable acceleration in fortunes has been that of West, who played the hard-drinking detective Jimmy McNulty in the show.

This year he was the lead on stage in the West End in the revival of Simon Gray's Butley; one of the central characters in the loudly praised TV drama series The Hour; and portrays the serial killer Fred West in a two-part ITV drama entitled Appropriate Adult. If Peters hasn't benefited quite so much from the Wire effect, he hasn't exactly been neglected, recently completing a leading role in Spike Lee's new film, as well as appearing in Simon's New Orleans saga, Treme, alongside fellow Simon regular Wendell Pierce (Bunk in The Wire).

Now, though, for the first time in four years West and Peters are appearing together in arguably the most inspired piece of theatrical casting since Nicole Kidman's tumescently acclaimed performance in The Blue Room. Peters is to play Othello and West Iago in Sheffield Theatres artistic director Daniel Evans's production of Othello at the Crucible, a venue that is perhaps less known for lines such as Iago's "green-eyed monster" than for the drama of green baize snooker.

Aside from the ongoing resonance of The Wire, the two actors also share an intimate connection to Sheffield. West grew up on the borders of the city and Peters, who must boast one of the most eclectic CVs in the business, spent a lot of time working in Sheffield. It was the place in which he began writing Five Guys Named Moe, his celebration of the jazz and blues composer Louis Jordan that became an unexpected West End stage hit in the 1990s.

A seasoned actor, Evans is a relative newcomer to directing but he has quickly established a reputation for bold and intelligent productions. West, who is not easily impressed by directors, believes that Evans is a director of the National Theatre in the making.

The director had the pair in mind for the roles right from the outset. He knew West a little (West was a year below him at the Guildhall drama school), and had long been an admirer of Peters. "I saw him playing Sky Masterson at the National and he oozed sex. I saw him in Howard Davies's production of The Ice Man Cometh in which he was absolutely true and alive. Not many actors can do plays and musicals and be equally brilliant."

Evans first approached Peters, only because he was unable to get in touch with the perennially busy West. "Before I was able to get the words Dominic West out of my mouth, Clarke said: 'Would you consider Dominic?' I said, 'That's exactly who I want.'"

It turned out that Peters had long harboured an ambition to play Othello, which he shared with several other members of the Wire cast.

"I think at one point Wendell [Pierce] brought it up," recalls Peters when I meet him and West during rehearsals in east London, "and we were all in the same mindset: this would be a really wonderful thing for us to do as we love each other's company, we know each other working, you can be as risky as you want to be."

"Actually," says West, subtly amending his co-star's memory, "what I think it was is that we had a lot of downtime on The Wire and at the beginning of every season we had great plans to do other stuff like put on a play. We'd have great plans and then we'd…" he pauses, as if searching for the right phrase, "get high."

The two of them let out great bellowing laughs of the kind that could effortlessly fill an auditorium. West, who famously went to Eton, wields a commandingly theatrical voice, of which he made inventive use in Butley. But even his extravagant vocal cords can seem thin and taut against Peters's mellifluous bass, a genial but authoritative sound that you could imagine belonging to God if He had soul. Listening to the recording afterwards, my own voice, by comparison with these pair of profundos, sounds as if I'd been abusing helium.

Pop trivia aficionados may know that it was Peters's honeyed baritone that interjects with "Oh give me love" in Joan Armatrading's classic "Love and Affection". I ask him if this is an urban myth, and he says no, it is indeed true and convincingly sings the line. "I think that's the right pitch too," he says with a satisfied smile.

Peters played Lester Freamon, the quiet and cerebral detective in The Wire, with a kind of gnomic understatement. The audience was left wondering about his background and how he came to be where he was. I mentioned that I read that he sought to tone down Freamon, make him a minimalist creation.

"That wasn't so much my choice…" he says.

"Doesn't sound like your choice," quips West.

"You see why I love to work with him," says Peters.

"Tone it down?" continues West with mannered theatrical bitchiness. "Not your first instinct."

Despite the implication that he doesn't need a second invitation to grab the spotlight, Peters is himself reminiscent in some ways of Freamon, at once friendly and mysterious, open and yet sublimely contained. He grew up in New Jersey, where he was the year above John Travolta at school, but left for Paris as a young man, living in Jean-Luc Godard's apartment during a period in which the French auteur was lending his support to black nationalists. And as the clown says in Othello, thereby hangs a tale.

"Were you a Black Panther?" teases West.

"No," replies Peters, going on to explain that Eldridge Cleaver, a leading Panther, had also stayed in Godard's apartment, at a different time, but that he never met either Cleaver or Godard. He did, however, meet James Baldwin, perhaps the most famous black American expatriate. He also began his stage career, taking over from his brother in a production of Hair.

A few years later he relocated to Britain, appearing in musical stage shows at such glamorous venues as the Watford Palace. The move from Paris to Watford is typical of a man who one moment is directing Denise Van Outen in a play, the next off to America to front a Spike Lee film. There's nothing precious about his approach. They're both jobs of work, and he's a man, you gather, who likes to work.

"On The Wire we always called him Four Jobs," says West, in reference to Peters's crammed employment schedule.

A kind of raucous camaraderie seems to inform the relationship between the Wire principals, fermented in experiences like the pre-Katrina trip to New Orleans – Wendell Pierce's hometown – that West, Peters and Pierce took for Mardi Gras. West claims that such was the level of indulgence that he has no memory of Mardi Gras itself.

"All I can remember is Lundi Gras and being on stage with George Clinton at the House of Blues."

"We were sitting up there watching George Clinton," Peters recalls, "and then we said, 'Where's Dominic?' Then someone said, there he is, on stage with George Clinton. He was bopping away. We were so drunk. Wendell had found this huge top hat and we were assaulting people in the street, asking rather large-hipped women to do this dance called 'Swing the Keys'. You just take a chain with keys on it," he helpfully explains, "and then they stick it in the back of their trousers and they swing their backsides to move the keys. It's quite exotic."

Pierce's name is frequently mentioned, and so I ask if he was ever considered for a part in the Othello production.

"There was a slight glitch at one point," says Peters, "and I did give him a call, as something else had come up for me that I wanted to do."

West turns askance to Peters. "Really?" he asks, genuinely surprised, and even a little outraged. "You never told me that! You would have ducked out?"

"I wouldn't have told you unless I really could do it," he replies calmly, "because I didn't want to put the willies up anybody until it was for sure."

"What was the job?" says West, ever the actor.

"I don't want to talk about it," says Peters firmly. "Let's just say it was paying a lot more money than this, and in a lot more exotic a location than Sheffield."

If Peters is known for his prodigious output, West is no slacker himself. When we meet, he is rehearsing in the day while in the evening he is still doing Butley, during which he is a fixture in every scene.

To commit a thousand lines of Shakespeare to memory while performing such a wordy role as Butley seems like a ruinously mighty effort.

"It is an extraordinary feat," Daniel Evans tells me later on the phone. "He must be so tired at the moment. Iago is the second biggest part in Shakespeare and he's not off stage in Butley. He has this huge range in which he has to be malevolent, he has to be funny. It's also psychologically hard to hold the two parts in your head and not let them bleed."

"I don't think it's the memory so much as the timing," says West. "I'm doing three weeks of performing at night. There's only five weeks of rehearsals. It's taken up a lot of time one would normally have for rehearsals or learning lines. So it's a bit of a gamble with me and one that I'm not sure I'm going to pull off."

"Oh you'll pull it off," says Peters, all avuncular reassurance. "We're both in the same boat in that respect. We could use another two weeks' rehearsal, particularly Dominic because of his schedule. But what he has to know is that I'm not going to let him fuck up and he better not let me fuck up. So if it takes me calling him at 11 o'clock to go through the lines, that's what we'll do."

Iago, of course, is a grand study in malice, a scheming, duplicitous, lying murderer of bottomless ingenuity. After Butley's egomaniacal nihilism and Fred West's sadistic psychopathy, it hardly seems like a respite from derangement. What attracted him to the part?

"Well I'm having a summer of villainy really," he says, as if resigned to his lot. "It seems to be the only roles I get offered now are scheming bastards."

In fact he's clearly pleased with the direction his career is taking. The last time I met him, three years ago, he was disillusioned with TV acting and talking about moving into directing. While he hasn't entirely abandoned that ambition, he now seems excited about the opportunities opening up for him – including Iago.

"He's the greatest villain ever written and one of the greatest parts in Shakespeare, so I couldn't really turn it down. I've always wanted to play him and I did the play for A-level and always thought it was a magical play."

Although the part was still coming together, West had made two key decisions when we spoke. He is going to play Iago with a Sheffield accent – while Peters will do Othello as he is meant to be, an African. "Maybe it's my prejudice but I think that a Yorkshire accent is one that's most associated with honesty, certainly among British playgoers," he says. "And the challenge with Iago is trying to make him appear honest. So that buys you a lot of honesty."

He also intends to bring out the acute sense of grievance that Iago feels at being overlooked by Othello for promotion. "Like McNulty, he's an aggrieved underling, raging against this bosses and thinks he's cleverer than his bosses. That's something everyone can relate to."

The last time I spoke to him, West had delivered a hilariously profane denunciation of an incompetent producer, so I wonder if it is something he in particular can relate to.

Peters curls up in silent giggles, nodding his agreement and the question's implication.

"Not particularly, no," says a slightly affronted West.

"Because he knows he's smarter than his bosses," Peters booms.

"No," West persists, "I think most people's experience is that they have to deal with pain-in-the-arse bosses who aren't as good at their jobs as they could be. And Iago is the archetype of the aggrieved lieutenant."

While West seems bombarded with offers to do evil, or at least obstreperous characters, Peters is more in danger of being viewed, as a result of the Freamon role, as the incarnation of quiet patience and moral decency, our very own Anglicised version of Morgan Freeman. Does he never yearn to be the bad guy?

"I was doing bad people up until Neil Jordan's Mona Lisa," he says, "and I remember sitting with Neil and saying I'm tired of playing the bad guy, the pimp or whatever. There was nothing I could show my kids. Constantly the black man was the bad guy. And in the script my bad guy got away and I said these people can't be seen to do that because it sends a message. Not only was I then killed in that film but I didn't work again for 10 years!"

"So 10 years later," says West, sticking up his arms in mimed defeat, "it's, 'Drug dealer, anyone?'"

The two of them fall into loud guffaws again, lending the impression that rehearsals are probably not weighed down by endless earnest discussions about the true meaning of the text. It's Peters who, gathering himself, returns to the original inquiry.

"One of the reasons I was drawn to Othello," he says, "is because of the virtue of the piece. There doesn't appear to be enough conversation about what is right and what is good. The world two weeks ago [he is referring to the riots] gave us a good idea about where we are now. So trying to find the benign way to be or search out his better qualities is what I'd like to do, though having said that the character I just got through playing with Spike is not a savoury character at all."

We fall into discussing the current state of British television drama, a subject I know is close to West's heart. I suggest that there was an almost palpable sense of relief behind the laudatory notices that The Hour drew, as if critics were grateful that Britain was still capable of producing well-made drama that wasn't too distantly buried in costume.

West thinks the system of writing is partly to blame. "The way it operates is that there is a lone auteur, whether it's Abi Morgan, Lynda La Plante or [Stephen] Poliakoff. There's always one lone genius. The reason I think The Wire was so great is that there was a lone genius backed up by seven great novelists. And the difference is mainly money. In The Hour we had one writer and six producers. In The Wire six writers and one producer."

I say that while money does make a difference, what really matters is a willingness to take a risk. There is money to produce an infinite number of limited TV dramas, but no one is prepared to invest in something long, panoramic and contemporary.

"Why not?" demands West.

"That's something you got to sort out," says Peters to West. "It's your voice. It's your time. It's the old guard."

"It's not the old guard," West bites back, "they're all younger than me. That's the problem: it's the young guard. The head of drama at the BBC is 32! If that. [Ben Stephenson is in fact 34]. Don't set me off on one."

We return to the less contentious issue of Othello, and in particular Daniel Evans. West's friend John Simm had told him how bowled over he had been by Evans's production of An Enemy of the People. So, I say, West had heard good things about Evans before working with him?

"Yes, but one always takes that with a pinch of salt," he says. "Maybe this is where I do get aggrieved with bosses."

Cue another burst of knowing laughter from Peters.

"Yes, I don't always love directors," West concedes. "But I love him."

"It's wonderful watching him in rehearsal," Peters agrees. "He's in everyone's mouth. He's really a wonderful character and allows us to throw a lot in."

Notwithstanding their anxiety about learning the lines in time, the pair believe it will be a memorable production which they hope to see staged in London too. The problem is they're both so tied up in work commitments that, should all go well, next May would be the earliest they could do it.

West is signed up to do the second series of The Hour and Peters is due to film the third series of Treme. Simon had promised West a directorial slot on Treme in the previous series but the actor was tied up filming the first series of The Hour. Does the offer still stand?

"I'm hoping, but again I'm filming The Hour at the same time. Actually," he says on a moment's reflection, "we finish about March. So round about Mardi Gras, funnily enough, I should be free."

If there were a stage note to bring this scene to a close, it would read: "Othello and Iago collapse together into deep and lusty laughter."

Othello opens at Sheffield Crucible on 15 September and runs to 15 October. www.sheffieldtheatres.co.uk; box office: 0114-249 6000