LOS ANGELES — Kumail Nanjiani loves ’90s romantic comedies, the mushier the better. “I started doing standup because of Hugh Grant’s best-man speech in ‘Four Weddings,’ which is basically a standup routine,” he said. For the aspiring comic, Mr. Grant was the gold standard of rom-com stars, although Mr. Nanjiani never dreamed of becoming one himself. “It just felt like the people who were making those things were, like, aliens, or gods,” he said.

Next month, Mr. Nanjiani tackles the lead role in the romantic comedy “The Big Sick,” based on his own experiences meeting, dating and making a hash of things with his future wife, Emily V. Gordon, who wrote the script with him. Mr. Nanjiani, 39, plays a gently tweaked version of himself, a Pakistani-American standup comedian and Uber driver; Emily (Zoe Kazan) is a therapist-to-be who heckles him — in a flirty, endearing way — during one of his sets. The relationship seems doomed from the start, seeing as how Mr. Nanjiani’s family expects him to marry a nice Pakistani woman, a fact he somehow neglects to mention to his new girlfriend. When Emily becomes ill and is placed in a medically induced coma — again, from real life — things come to an unexpectedly funny head.

Seeing a Pakistani-American comic secure the romantic lead in a Hollywood film would be a rare delight under any circumstances. But what makes “The Big Sick” all the more remarkable is how little fuss is made of it. In the film, we see Kumail and his family eating and laughing and goofing off, fighting and (after a spell) making up, just like the actor’s real family. It’s a vision of a Muslim family, Mr. Nanjiani notes, rarely seen in American film.

“You just don’t see Muslims being matter-of-fact Muslim,” he said. “They’re always defined by their Muslim-ness. We’re either terrorists, or we’re fighting terrorists. I remember seeing ‘True Lies’ and going, why are we always the bad guys?”