Langella, an Italian American, was born in Bayonne, New Jersey, the son of Angelina and Frank A. Langella Sr., a business executive who was the president of the Bayonne Barrel and Drum Company. Langella attended Washington Elementary School and Bayonne High School in Bayonne. After the family moved to South Orange, New Jersey, he graduated from Columbia High School, in the South Orange-Maplewood School District, in 1955, and graduated from Syracuse University in 1959 with a Bachelor of Arts degree in drama. He remains a brother of the Alpha Chi Rho fraternity.
Langella appeared off-Broadway (e. g. in The Immoralist at the Bouwerie Lane Theatre in 1963, and Robert Lowell's The Old Glory in 1965) before he made his first foray on a Broadway stage in New York in Federico García Lorca's Yerma at the Vivian Beaumont Theater, Lincoln Center, on December 8, 1966. He followed this role by appearing in William Gibson's A Cry of Players, playing a young, highly fictionalized William Shakespeare, opposite Anne Bancroft at the same venue in 1968, and won film fame in two 1970 films: Mel Brooks' The Twelve Chairs and Frank Perry's Diary of a Mad Housewife, being nominated for a Golden Globe Award for Most Promising Newcomer for the latter. Langella won his first Tony Award for his performance in Edward Albee's Seascape and 1975 and was nominated again for what may have been the performance for which he was best known in the early part of his career: the title role of the 1977 Broadway production of Dracula. 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. He eschewed the career of a traditional film star by always making the stage the focal point of his career, appearing on Broadway in such plays as Strindberg's The Father (winning a Drama Desk Award), Match (Tony Award nomination), and Fortune's Fool, for which he won a second Tony Award.
But Langella would continue to juggle film and television with his stage work, playing Sherlock Holmes in a 1981 adaptation of William Gillette's play Sherlock Holmes. He repeated the role on Broadway in 1987 in Charles Marowitz's play Sherlock's Last Case. That same year, Langella would also portray the villain Skeletor in Masters of the Universe, which he has described as one of his favorite roles. In 1988, Langella co-starred in the film And God Created Woman. In 1993, he made a three-episode appearance on Star Trek: Deep Space Nine as the devious Jaro Essa. He 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. On film, he played Clare Quilty in Adrian Lyne's adaptation of Lolita and appeared as a villainous pirate in the summer 1995 release Cutthroat Island. His film work also includes roles in George Clooney's Good Night, and Good Luck (2005) as former CBS chief executive William S. Paley and Bryan Singer's Superman Returns (2006) as Daily Planet editor Perry White. Langella received critical acclaim as well as the Boston Society of Film Critics Award in 2007 for his sensitive portrayal of an elderly novelist in Starting Out in the Evening.
He was cast as Richard Nixon in Peter Morgan's Frost/Nixon, which received enthusiastic reviews during a run at the Donmar Warehouse and Gielgud Theatre in London before moving to New York's Bernard B. Jacobs Theater in April 2007, culminating in Langella's third Tony Award. He reprised the role of Nixon in the 2008 Oscar nominated Best Picture film Frost/Nixon, directed by Ron Howard. He received Golden Globe, Screen Actors Guild, and BAFTA nominations for Best Actor for his performance. He was also nominated for an Academy Award in the Best Actor category for the role, losing to Sean Penn's performance in Milk.
In 2000, he played the role of Ebenezer Scrooge in a musical version of A Christmas Carol at Madison Square Garden. He has also appeared in notable off-Broadway productions, including in the title role of Robert Kalfin's Chelsea Theater Center production of The Prince of Homburg, which was filmed by PBS for the Theatre in America series. He starred as Sir Thomas More in the 2008 Broadway revival of A Man for All Seasons.
In late 2009, he starred alongside Cameron Diaz and re-united with Superman Returns co-star James Marsden in the Richard Kelly film The Box. Langella starred in the drama thriller Unknown, which was directed by Jaume Collet-Serra, and was released in 2011.
In October and November 2013, Langella played King Lear at the Minerva, Chichester Festival Theatre in Chichester, UK. It travelled to the Harvey Theater at the Brooklyn Academy of Music in New York in 2014. In 2016, he played the title role in Doug Hughes' production of the US premiere of Florian Zeller's play The Father at the Samuel J. Friedman Theatre on Broadway.
Langella was married to Ruth Weil from June 14, 1977 to their divorce in 1996. They have two children. He also then lived with actress/comedian Whoopi Goldberg, whom he had met on the set of Eddie. From 1996 they were together but they separated in March 2001. Langella published a memoir in 2012 called Dropped Names: Famous Men and Women As I Knew Them. In a review in the New York Times Book Review, Ada Calhoun wrote that "Langella's book celebrated sluttiness as a worthy—even noble—way of life. There was so much happy sexuality in this book that reading it was like being flirted with for a whole party by the hottest person in the room. It was no wonder Langella was invited everywhere."
Langella's awards include two Obie Awards in 1965 for Best Performance in the play The Old Glory by Robert Lowell and for Distinguished Performance in John Webster's play The White Devil that same year, a Tony in 2002 for Best Supporting Actor in Ivan Turgenev's Fortune's Fool, and Tonys for Best Featured Actor in a Play in 1975 for Edward Albee's Seascape, and for Best Leading Actor in a Play in 2007 for Peter Morgan's Frost/Nixon, and in 2016 for his role as André in The Father. He also received an Academy Award nomination for Best Actor in a Leading Role for his performance as Richard Nixon in the film Frost/Nixon (2008). Langella was nominated for two other Best Leading Actor in a Play Tonys: first in 1978 for the Edward Gorey-designed revival of Bram Stoker's Dracula and again in 2004 for Stephen Belber's Match. In 2002, Langella was inducted into the American Theater Hall of Fame.