Between 1997-99, Harris made his professional debut in the national tour of Rent, starring as indie filmmaker Mark Cohen. He returned to the show in 2010 as the director of a production at the Hollywood Bowl, featuring Wayne Brady, Aaron Tveit, Skylar Astin, and Vanessa Hudgens in the star-studded cast.

Harris played the role of childlike urchin Tobias “Toby” Ragg in Stephen Sondheim’s Sweeney Todd on numerous occasions between 1999 and 2001: with the New York Philharmonic, with the San Francisco Symphony Orchestra, and at Los Angeles’s Ahmanson Theatre and Ravinia Festival. The New York concert, starring George Hearn in the title role and Patti LuPone as Mrs. Lovett, was filmed for posterity.

Harris made his Broadway debut in David Auburn’s play Proof in 2002, about the daughter of a recently deceased mathematical genius. Harris took over the role of former graduate student Hal, becoming the third of four people to play him throughout the Tony Award and Pulitzer Prize-winning show's two-plus-year run.

Proof later became a 2005 film starring Gwyneth Paltrow and Jake Gyllenhaal, and its first Broadway revival debuts in 2026 starring Ayo Edebiri and Don Cheadle.

Sam Mendes and Rob Marshall’s production of Cabaret at Studio 54 featured a revolving door of talent in the lead roles throughout its 2,377 performances, making it the third longest-running revival in Broadway history. In 2003, Harris took over role of the Emcee opposite Molly Ringwald and then Deborah Gibson as Sally Bowles.

Nearly 15 years after its 1990 Off-Broadway debut, Sondheim’s cult classic musical Assassins received its Broadway debut at Studio 54 in 2004, directed by Joe Mantello. Harris played a narrator called the Balladeer, who, toward the end of the show, morphs into Lee Harvey Oswald, assassin of John F. Kennedy.

One of the production's most striking moments was how the film of Kennedy’s assassination was projected onto Oswald’s T-shirt. Assassins won five Tony Awards, including Best Musical Revival, and Harris reprised his performance in a one-night benefit concert for Roundabout Theatre Company in 2012.

Talk about a full-circle moment. Harris made his professional stage debut in Jonathan Larson's Rent, and he made his London debut as a fictionalized version of Larson in the U.K. premiere of his autobiographical musical tick, tick... BOOM! The production took place at the intimate, prestigious Off-West End Menier Chocolate Factory in 2005.

In 2024, Harris directed the musical at the Kennedy Center in Washington D.C., where Brandon Uranowitz starred as Larson.

Ironically, in one episode of the first season of the musical TV show Glee, Harris guest stars as an anti-theatre character: Bryan Ryan, a former classmate of Will Schuester's intent on cutting funding for the glee club. He still sang, though, delivering performances of Aerosmith's "Dream On" and Billy Joel's "Piano Man."

Harris starred as Bobby, a 35-year-old NYC bachelor surrounded by married friends, in Lonny Price’s semi-staged concert of Sondheim’s concept musical at the New York Philharmonic in 2011. The cast also included Patti LuPone as Joanne, Martha Plimpton as Sarah, and Stephen Colbert as Harry, and the concert was filmed for PBS and later released on DVD.

In 2014, Harris had one of his biggest stage successes to date when he played the title role in the first Broadway production of Stephen Trask and John Cameron Mitchell’s 1998 rock musical Hedwig and the Angry Inch. Hedwig Robinson is a fictional genderqueer German glam rocker inspired by David Bowie, John Lennon, and the punk artists Lou Reed and Ziggy Pop.

Harris won the Tony for Best Leading Actor in a Musical, and the show won for Best Musical Revival. New York Theatre Guide’s reviewer observed, “Watching Neil Patrick Harris in this show is like watching an explosion in slow motion, something along the lines of the Big Bang.”

After an eight-year absence from the stage, Harris returned to Sondheim as the Baker in New York City Center's 2022 Encores! production of Into the Woods, a musical assembled from various fairytales. When Lear deBessonet’s concert production transferred to Broadway, Brian d’Arcy James took over Harris's role, while Sara Bareilles continued as the Baker’s Wife.

Following a short run in Peter Pan Goes Wrong and a one-night cameo in Gutenberg! The Musical! on Broadway in 2023, Harris appeared off Broadway at MCC Theater in Robert O’Hara’s play Shit. Meet. Fan. in 2024. Based on the 2016 Italian film Perfect Strangers, the explosive drama about friendships put to the test had a starry cast also featuring Jane Krakowski, Debra Messing, and Constance Wu.

Harris appears in his first full-length Broadway run in over a decade in a revival of Yasmina Reza’s modern classic Art. Harris plays Serge, who buys an expensive all-white painting that his friend Marc (Bobby Cannavale) thinks is terrible, and Yvan (James Corden) ends up caught in the middle. Having begun his stage career in Rent, in which art and friendship are also central, Harris comes full-circle with this Tony Award-winning play.

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