She is known for her portrayal of Safar Khan in the HBO drama miniseries The Night Of, as well as for her role as Nalini Vishwakumar in the Netflix teen comedy series Never Have I Ever.

Jagannathan also co-conceived, produced, and acted in the play Nirbhaya,[2] which was considered "one of the most powerful and urgent pieces of human rights theatre ever made," and is regarded as a critical moment in India's history of women's empowerment.

She earned a scholarship to pursue a Master of Fine Arts in acting at the Actors Studio Drama School at Pace University.

Before her career as an actor, Jagannathan spent 15 years working in advertising at agencies like TBWA\Worldwide, Ogilvy, and Deutsch Inc. before starting her own consultancy, Cowgirls & Indians.

The Village Voice said that "the most enjoyably subversive element is Poorna Jagannathan as the self-sufficient bachelorette who waylays Tashi on his way to the altar.

Rangy, corkscrew-haired, with a wary demeanor that can't long be upset by anything, she's a happy departure from the usual run of Xeroxed, pedestaled beauties.

"[14] The Daily News and Analysis said that Jagannathan shines in the film, and that "her bohemian sex appeal" is "a refreshing change from the prim and proper 'heroine' we are used to watching.

Sonia Saraiya from Vanity Fair said, "I've seen a lot of actors attempt to flesh out the stereotypically demanding Indian mom, but I've never seen anyone do it as well as Jagannathan does...

In 2018, Jagannathan lent her voice to three podcasts in the Good Night Stories for Rebel Girls series, based on The New York Times Best Seller list books by Elena Favilli and Francesca Cavallo.

[25] Moved by a gang rape and murder in Delhi on December 16, 2012, Jagannathan initiated, produced, and acted in a testimonial play called Nirbhaya (transl.

[30][31][32][33] In March 2014, Nirbhaya was the centrepiece performance for Southbank's "Women of the World" festival where it played to sold-out houses in the United Kingdom.