The history of hip-hop is full of dynamic duos, but few are as enigmatic and inimitable as Run the Jewels. Comprised of two long-standing industry veterans, Killer Mike (né Michael Render) and Jaime “El-P” Meline, Run the Jewels delivers unflinching and acerbic political critique, as well as a healthy dose of goofy Cheech and Chong-style humor, often in the same breath.

The most recent of three albums, “Run the Jewels 3,” is both the strongest work and the most poignant. Tackling a range of social issues, from the nascent presidential administration to police brutality and inner-city gentrification, it conjures a world where gallows humor reigns supreme. “Went to war with the devil ... he wore a bad toupee and a spray tan,” Render raps over a murky beat on “Talk To Me,” effectively summarizing the group’s aesthetic.

Yet while the virtuosic flow may seem effortless, Run the Jewels’ story is one of improbable success and a friendship that runs far deeper than the music itself.

Render and Meline, both on the cusp of middle age, have been hustling in the music industry for decades. Render, who is from Atlanta, has put out a half dozen albums and made guest appearances with artists like OutKast. Meline, who grew up in Brooklyn, once ran the Definitive Jux label and produces records for countless hip-hop artists.

After collaborating on one of Render’s albums, they began work on a whimsical set of songs, with no anticipation of success, that eventually became their 2013 self-titled debut. “When we first came out, we were 90 percent jokes,” El-P says of their traded verses.

“My muse is my friendship with Mike,” he continues. “There’s only one person that I want to connect with when I’m making records, and that’s Mike.”

For their sophomore release, simply titled “Run the Jewels 2,” they found themselves using Run the Jewels — which had quickly amassed an ardent fan base — as a vehicle to vent their anger with what they saw as a broken political system and a society rife with injustices. “It takes a toll on your psyche to see black men killed every month on television,” Render says.

Cannabis activism is another issue near to their hearts. On the track “Early,” the duo, both avid consumers — to put it lightly — unspools a devastating cautionary tale that begins with Render getting arrested on his front lawn for smoking pot.

“Man, I’m tryin' to smoke and chill, Please don’t lock me up in front of my kids / And in front of my wife,” he raps. “You do this and you ruin my life.”

“They’ll watch you walk to the store they’re recording / But didn’t record cop when he shot, no warning,” Meline adds later in the song.

Render in particular is committed to speaking out about social justice off the stage. Beyond championing Bernie Sanders during the 2016 presidential campaign, he has drawn attention to several issues, including the racial inequality in the exploding cannabis industry.

As states legalize cannabis throughout the United States, people convicted of nonviolent drug crimes, who are disproportionately people of color, are often disqualified from participating in the marijuana industry. As BuzzFeed reported last year, “Fewer than three dozen of the 3,200 to 3,600 storefront marijuana dispensaries in the United States are owned by black people — about 1 percent.”

Render has taken notice of California’s new laws, which intend to expunge the records of low-level drug offenders.

“It is imperative that the people most in need of a second chance actually get one,” he wrote recently in Rolling Stone. “The price they have already paid for our failed drug policy is steep enough.”

Perhaps more than any artist in 2017, Run the Jewels have put their finger on the existential crises plaguing America’s disenfranchised, angry and scared citizens. Yet their greatest skill may be balancing that heaviness with a levity that speaks to the joy they get from making music together. “To separate those things would not be giving you who we are,” El-P says.

“I am not a pessimist. Nor am I a f— idiot,” he continues. “Do I think justice wins every time? I do not. I believe in the triumph of goodness in people’s hearts.”

Max Savage Levenson is a freelance writer. Email: datebook@sfchronicle.com

Run the Jewels: 8 p.m. Saturday, July 22, Bill Graham Civic Auditorium, 99 Grove St., S.F. $50 and up.