Mankiewicz was born in Los Angeles on June 1, 1942. His parents were Austrian-born Actress Rose Stradner and the celebrated screenwriter/director Joseph L. Mankiewicz. In 1950, his father, after winning four Oscars in two years for the screenplays and direction of A Letter to Three Wives and All About Eve, decided to move his family back to New York City, where he had been raised, the son of a German immigrant language professor.

Mankiewicz was a graduate of Phillips Exeter Academy (1955–59) and Yale College (1959–63). He majored in drama at Yale, completing the first two years of the Yale Drama School while still an undergraduate.

During vacations he worked at the Williamstown Summer Theater in Massachusetts both in production and as an actor. In 1961, he was hired as a third assistant Director on The Comancheros, a film starring John Wayne and Lee Marvin, which was shot in the Monument Valley of Utah, the last film directed by Michael Curtiz. Wayne told Mankiewicz to remove his John F. Kennedy button.

In 1963, two young producers, Stuart Millar and Lawrence Turman, took Mankiewicz on as their assistant while making The Best Man, the 1964 film version of Gore Vidal’s Broadway play starring Henry Fonda. He was involved in virtually every aspect of the film, receiving his first on-screen credit as “Production Associate.”

In 1967, Mankiewicz joined forces with a friend, Jack Haley Jr. to come up with a musical television special tailored for the then hugely popular Nancy Sinatra: Movin' with Nancy, co-starring Frank Sinatra, Dean Martin, Sammy Davis Jr. and Lee Hazlewood. Mankiewicz was the sole Writer and Haley won the Emmy for directing. This was followed by The Beat of the Brass, starring Herb Alpert and the Tijuana Brass in 1968.

The combination of that screenplay and the TV specials led Broadway Producer Fred Coe to ask Mankiewicz to write the book for Georgy!, the musical version of the film Georgy Girl. It opened at the Winter Garden Theatre in 1970, was nominated for three Tony Awards, but closed after four performances.

In 1975, Mankiewicz wrote the screenplay for Mother, Jugs and Speed, a dark comedy about ambulance drivers starring Bill Cosby, Raquel Welch and Harvey Keitel. He co-produced the film with Director Peter Yates who later asked Mankiewicz to come to the British Virgin Islands to do a major rewrite on Yates’ next film, The Deep, with Robert Shaw and Jacqueline Bisset. The film was a huge box office success and cemented Mankiewicz’s reputation as a “script Doctor.”

In 1977, Director Richard Donner was hired to direct Superman: The Movie and Superman II. At the time the script drafts combined were more than four hundred pages long (an impossible length to shoot) and Donner felt they were much too campy as well. He brought Mankiewicz aboard to do a complete overhaul in terms of length, dialogue and tone. Mankiewicz stayed on the production for more than a year, assisting Donner in other departments as well. Donner gave Mankiewicz a separate credit in the main title sequence: "Creative Consultant." The Writer’s Guild strenuously objected on two grounds; first, that the traditional script arbitration process was being bypassed and second, that Mankiewicz’s credit came after the original screenwriters and not before them, implying that his contribution was more important. The dispute went to a legal hearing. Mankiewicz won. His credit remained where it was on Superman: The Movie, but he agreed to have it come just before the listed screenwriters on Superman II.

Mankiewiz was unhappy at Warner Bros and he decided to move over to Universal. "The last thing I wanted to do was make another deal that cast me as a fixer," he said. "And Frank Price, who was then running production, agreed totally. So after two weeks here, Frank asked me to do a rewrite on the Dragnet script!" However it worked out well for Mankiewicz, who got along well with co Writers Dan Aykroyd and Alan Zweibel, and he wound up directing Dragnet. It was one of the top grossers of 1987, and marked his feature debut as Director.

Mankiewicz's career slowed down in the 1990s. He later claimed he had been unofficially blacklisted when he left his agency, CAA.

In 2006, The Dodge College of Film and Media Arts at Chapman University invited Mankiewicz to be their "Film Maker in Residence." He stayed on as a Trustee Professor, teaching a course in film making to their graduate students.

He died at his home in Los Angeles from pancreatic cancer on July 31, 2010.

In May 2012, My Life as a Mankiewicz was published. Written in collaboration with Robert Crane, the book was largely completed at the time of his death, but finished by Crane and published by the University Press of Kentucky.

Mankiewicz remained active in the Writer’s and Director’s Guilds and was a former member of the Board of Governors of the Motion Picture Academy of Arts and Sciences.