His reprisal of the Nixon role in the film production of Frost/Nixon directed by Ron Howard earned him an Academy Award nomination for Best Actor.

[9] Langella appeared off-Broadway (in The Immoralist at the Bouwerie Lane Theatre in 1963[10] and Robert Lowell's The Old Glory in 1965 among other shows) before he made his first foray onto a Broadway stage in New York in Federico García Lorca's Yerma at the Vivian Beaumont Theater, Lincoln Center, on December 8, 1966.

[11] The same year, he also appeared in Frank Perry's Diary of a Mad Housewife, being nominated for a Golden Globe Award for Most Promising Newcomer.

Despite his initial misgivings about continuing to play the role, he was persuaded to star opposite Laurence Olivier in the subsequent film version directed by John Badham.

During this time he also acted in Passion in 1983, Noël Coward's Design for Living in 1984, Arthur Miller's After the Fall in 1984, and David Rabe's Hurlyburly in 1985.

In 1993, he made a three-episode appearance on Star Trek: Deep Space Nine as the devious Bajoran Minister Jaro Essa.

He also played a supporting role in the Ivan Reitman comedy Junior alongside Arnold Schwarzenegger, Danny DeVito, and Emma Thompson.

[14] Langella also appeared as Al Baker in "Dominance", a 2003 episode of Law & Order: Special Victims Unit and had a recurring role as Pino in the 2005 short-lived sitcom Kitchen Confidential.

[15] He was cast as Richard Nixon opposite Michael Sheen in Peter Morgan's play Frost/Nixon, which received enthusiastic reviews during a run at the Donmar Warehouse and Gielgud Theatre in London before moving to Broadway in New York's Bernard B. Jacobs Theater in April 2007.

He was also nominated for an Academy Award in the Best Actor category for the role, losing to Sean Penn's performance in Milk.

[16] In 2010, he played Louis Zabel in Oliver Stone's Wall Street: Money Never Sleeps, alongside Michael Douglas, Shia LaBeouf, and Carey Mulligan.

[17] In 2012, he earned critical praise for his role in the independent film Robot & Frank, with Peter Travers of Rolling Stone magazine calling his performance "a masterclass in acting".

Langella also played Cleveland Browns owner Anthony Molina in the movie Draft Day, which also starred Kevin Costner, Jennifer Garner, and Dennis Leary.

In 2015, Langella joined the cast of FX's critically praised drama The Americans with Keri Russell and Matthew Rhys.

[21] That same year, he appeared in Captain Fantastic with Viggo Mortensen and was again nominated with the ensemble cast for the Screen Actors Guild Award.

In 2022, following investigations into claims of sexual harassment on set, Langella was fired from The Fall of the House of Usher and replaced by Bruce Greenwood.

[22] In a guest column for Deadline, he claimed to have been "canceled" and denied allegations of unacceptable behavior while telling his version of events; this included calling cast members "baby" or "honey", in addition to describing guidance from an intimacy coordinator as "absurd" and ultimately going against the agreed blocking for a scene, leading his scene partner to walk off set.