She began her career on television, starring as a grief counselor in the NBC crime drama series Crossing Jordan (2001–2007).

Hahn gained prominence appearing as a supporting actress in a number of comedy films, including How to Lose a Guy in 10 Days (2003), Anchorman: The Legend of Ron Burgundy (2004), Step Brothers (2008), Our Idiot Brother (2011), We're the Millers and The Secret Life of Walter Mitty (both 2013), and Glass Onion: A Knives Out Mystery (2022).

She voiced Ericka Van Helsing in two films of the Hotel Transylvania franchise (2018–2022) and Doctor Octopus in Spider-Man: Into the Spider-Verse (2018).

For starring in the Hulu series Tiny Beautiful Things (2023), she received a nomination for a Primetime Emmy Award for Outstanding Lead Actress.

Afterward, she earned her MFA in drama from Yale University,[12] where she starred as Sally Bowles in Cabaret and as Célimène in Molière's play, The Misanthrope.

She appeared with the Huntington Theater Company's productions of Jon Robin Baitz's Ten Unknowns and Sidney Kingsley's Dead End, and had parts in the Williamstown Theatre Festival's productions of William Shakespear's A Midsummer Night's Dream and Hamlet, John Guare's Chaucer in Rome, and Henrik Ibsen's Hedda Gabler.

[13] In 2024, Kathryn Hahn delivered the commencement address to Northwestern University’s graduating class and received an honorary Doctor of Arts degree.

[15][16] Hahn's first appearance on television was in Hickory Hideout, a local puppet show for children for then-NBC owned-and-operated station WKYC in Cleveland.

From 2012 to 2015, she received praise for her recurring role on the NBC comedy series Parks and Recreation as Jennifer Barkley, the campaign manager of Leslie Knope's (Amy Poehler) opponent Bobby Newport (Paul Rudd).

[24] In 2013, Hahn played her first leading role, in the comedy-drama film Afternoon Delight, which was written and directed by Joey Soloway.

In 2014, Hahn was cast as Rabbi Raquel Fein in the Amazon Studios critically acclaimed dark comedy-drama Transparent, whose creator, Joey Soloway, had directed her in Afternoon Delight.

[29] That year Hahn co-starred in the science-fiction adventure film Tomorrowland,[30] and starred in the box-office horror hit The Visit.

[36] IndieWire's Kate Erbland gave the film a B−, noting that it "boasts some good jokes but Hahn's revelatory performance is the big draw."

First, Hahn provided the voice of character Ericka Van Helsing in the comedy Hotel Transylvania 3: Summer Vacation.

[51] That same year, Hahn began voicing Paige Hunter in the Apple TV+ animated musical comedy series Central Park.

[52] In 2021, Hahn joined the Marvel Cinematic Universe by starring in the Disney+ limited series WandaVision as Agnes, a mysterious "nosy neighbor", later revealed to be Agatha Harkness.

[58] She played Jo Polniaczek in The Facts of Life segment of the third edition of Live in Front of a Studio Audience on December 7, 2021.

[64] The same month, it was announced that she would star in the upcoming Hulu limited series Tiny Beautiful Things based on the bestselling book by Cheryl Strayed.

[65] On April 7, 2023, Hulu released all eight episodes of Tiny Beautiful Things, in which Hahn starred in the lead role of Clare.