The sweet, sixtysomething couple in pastel leisurewear are curious about the room next to theirs in this Santa Monica beachfront hotel. There have been a lot of comings and goings all day. "So much activity!" the woman chuckles to me while her husband approaches the studio publicist who is loitering alongside us in the hallway. "So – who ya got in there?" he asks conspiratorially. "Julia Louis-Dreyfus," the publicist smiles. Their jaws loosen noticeably and they take a single deferential step backwards. They might not have seen Louis-Dreyfus as Selina Meyer, the vice-president grappling with her own political impotence in Armando Iannucci's profane sitcom Veep, for which she has won a brace of Emmy bookends. And her new film, the warm, wise romantic comedy Enough Said , has only just opened. But don't underestimate the enduring voodoo power of her nine years on the most masterful and abrasive sitcom ever made: Seinfeld. For many millions of people (particularly in America, where the phrase "cultural phenomenon" is too measly to describe the show's reach) she will for ever be Elaine Benes, the most achingly desperate of the Seinfeld quartet.

"What's she like?" the wife asks. "She's lovely," the publicist confirms, to appreciative cooing. I smile too, recalling some of the lines that Louis-Dreyfus delivers in the new series of Veep: "Jolly Green Jizz-Face …" "Why don't you put on your running shoes and get to the fucking point?" "I'd rather set fire to my own vulva …" Lovely indeed.

Enough Said is gentler than Veep, but no less probing in its own way. Louis-Dreyfus plays Eva, a massage therapist and single mother bracing herself for her daughter's imminent move to university. In her discombobulated state, she slides into a tentative romance with a hulking TV archivist (the late James Gandolfini). The movie feels rooted in the specific epiphanies of middle age. "Well, it's about the fear of failure," explains Louis-Dreyfus in her suite. She lounges on the mushroom-coloured sofa, propping herself up on one elbow in a loose white blouse patterned with flowers. "I suppose that kind of fear could be an issue at any age. But it's pertinent to this woman at this moment. She's facing this possible vast landscape of loneliness and it's so paralysing that it fuels some bad decision-making and blurs lots of her boundary issues."

Julia Louis-Dreyfus as Elaine Benes with her co-stars in the masterful and abrasive sitcom Seinfeld. Photograph: Rex Features

In Seinfeld's fourth series, Elaine was described as "a pretty woman, you know – kinda short, big wall of hair, face like a frying pan." Some of those descriptions need revising if they are to be applied to Louis-Dreyfus now. At 52, she's still crisply pretty, but her hair is straight and dark, rather than high and frizzy. And I don't spot in her expression that devastating sourness with which Elaine could drop a man at 40 paces. But it takes a while to get used to her habit of stopping dead when she has finished a thought, with none of the space-filling blather to which some of us are prone. Her comic style is precise and low-fat. So, too, is her conversation.

She starred in another project recently about a similar subject to Enough Said – Picture Paris, a short film by her husband, Brad Hall, whom she met at university. The thematic overlap is a coincidence, she insists, though it does pertain to her circumstances. The elder of the two sons she has with Hall is currently at university. "In our family's life the moment of his departure was pivotal. It undid us in a big way that I wasn't prepared for – but also, I kind of was. It's just more jarring than you expect. The reality of them leaving is hard to digest emotionally."

Eva seems contented with middle-age itself. How is it working out for Louis-Dreyfus? "I actually dig it. It's funny because I don't think of myself as middle-aged. In my mind, I'm, like, mid-30s. However: I also really like being here now and having all these experiences behind me. I like that. I find it very freeing. When you're younger you're putting yourself out there in a way you think you should be seen. Then as you get older you're like: 'Nah, fuck that.'"

Julia Louis-Dreyfus at the London film festival premiere of Enough Said. Photograph: Ben Stansall/AFP/Getty Images

The new picture would have been admired whenever it was released, but coming in the wake of Gandolfini's death makes it especially poignant. His performance is immensely delicate. "That's what he was like," she says, sitting forward. "I liked him immediately and I think he felt the same way. We had a good chemistry from the get-go. He's an amazing actor. He really is a gentle giant." Her use of the present tense is striking. "I really wish he was sitting here next to me and we could talk to you together about the movie. It's a tragedy that he isn't." She breaks eye contact and stares at the carpet, her voice wavering. "The film is something to celebrate. I just feel overcome with gratitude that I got to work with him."

And it does mean, I point out, that she has now had screen romances with two of the scariest men in television. I'm referring to Tony Soprano and Breaking Bad's Walter White: on Seinfeld, Elaine had an on-off affair with Tim Whatley, the dentist who converts to Judaism for the jokes, which provided an early role for Bryan Cranston. "Oh yeahhhhh!" she cries. "That's fantastic." A recent New Yorker profile painted Cranston as quite the model of actorly intensity. "I don't remember him being intense. Just very funny. For a long time after, whenever I saw him I'd always call out: 'Hey, Tim WHAT-ley!'" She pulls a guilty face, aware perhaps of how childish this might sound. "I don't do that any more. Maybe he'd get a kick out of it ..."

When she joined Seinfeld for its second episode in 1990, she had under her belt an unhappy three-year spell on the US sketch show Saturday Night Live, where her husband was also in the cast. "I was not getting a lot of air time on SNL. I was young and inexperienced and I went in with no idea of how to navigate that universe, which was not very female-friendly." In her final year, Seinfeld's future co-creator Larry David joined the writing staff, only to quit after failing to get a single sketch on air during his tenure. "We were both equally miserable and we bonded over that. That's where Larry lives: in discomfort. It's where most comedy comes from. Discomfort is a very underrated feeling."

I wonder if she realised at the time how radical a creation Elaine was. It seems incredible now that a woman in a prime-time 1990s network sitcom was permitted to be as funny and venal as her male co-stars. Elaine broke every taboo. She was anti-religion, pro-abortion and an appalling dancer. Sexually she was unapologetically ravenous, even undiscerning; in one episode, a period of enforced celibacy rendered her temporarily insensible. She enjoyed her promiscuity so that the women in Sex and the City and Girls could later do likewise.

For Louis-Dreyfus, the most significant advance occurred during The Contest, an episode in which the main characters attempt to abstain from self-abuse. "That was groundbreaking. Guys talking about masturbation was acceptable. But when a woman enters that dialogue, it's a whole different matter. I felt lucky to be a part of that. To me, it was the show that was radical rather than Elaine. It was an anti-sitcom sitcom. 'You mean all these little moments build up to become a show about – that? Seriously?'"

Simon Blackwell, a writer and producer on Veep, says Louis-Dreyfus is a connoisseur of comedy. "She cares about it, as a craft," he tells me. "She's great on the mechanics of comedy, the nuts and bolts of how it works. That stuff fascinates her – how an extra beat of time can nail a joke or kill it. Why that word should go in that place in the sentence, or when you need to break the sentence. Matt Walsh, who plays Mike in Veep, says she can find the extra jokes on the way to the joke, and that's true. It's almost an academic interest, or like a musician knowing theory."

Louis-Dreyfus spent a decade or so after Seinfeld trying on different sitcoms for size. But it was Veep, currently preparing for a third series, that provided her with the first part forceful and complex enough to rival Elaine. As Selina, she strides purposefully, arms pumping in front of her like pistons; she dishes out insults and invective the way other people pass around breath-mints. I express concern that Selina hasn't yet enjoyed enough moments of triumph: how much humiliation can one character take? "Absolutely," she says. "And that's coming. Triumph is great because where do you go from there? Down. That's good for comedy."

"She's such a joy to write for," says Blackwell. "You can give Julia anything to do and she'll nail it. It's like this comedic five-octave range. She's a great, great physical comedian but she can also bring it down to this laser-surgery level. I remember when we did episode two of season one of Veep and there's a scene where Selina is told the president is having chest pains and she has to get to the White House situation room – she thinks she's about to become president. Her line was 'I'm so sorry' and the stage direction in brackets was 'trying not to smile'. And it's one of the funniest things I've ever seen – she plays so many emotions with just her eyes, it's astonishing. It's this really small performance, but so precise it gets a huge belly laugh. And she gave us so many options to choose from in the edit, each one different by just a hair. Incredible."

Dreyfus as Selina Meyer in Veep. Photograph: Bill Gray/AP

The fluid, improvisatory style of working on Veep provides part of the appeal for her. "You're never quite sure what you're going for but you just have to go for it anyway," she says. But the intervening decades between Seinfeld and Veep haven't stifled her famous tendency to corpse during filming. There was even an entire Seinfeld episode (The Pez Dispenser) devoted to Elaine's inability to suppress her laughter. "It still happens," she chuckles. Very soon that chuckle builds to a laugh, and from there to a mildly disconcerting hyuk-hyuk-hyuk. She's cracking up over the idea of cracking up. "If I get tired, I'm a goner," she says eventually. "But it's also a good sign. It means I'm enjoying the movie or TV show I'm making. I'm its greatest fan!" This sets her off again. "That is gonna look really bad in print. You really gotta spin it right, man, because otherwise it's gonna make me sound like such an asshole."

• Enough Said is on release. Veep series two is on Sky Atlantic.