Pakula started his Hollywood career as an assistant in the cartoon department at Warner Brothers. In 1957, he undertook his first production role for Paramount Pictures. In 1962, he produced To Kill a Mockingbird, for which he was nominated for a Best Picture Academy Award. Pakula had a successful professional relationship as the Producer of movies directed by Robert Mulligan from 1957 to 1968. In 1969, he directed his first feature, The Sterile Cuckoo, starring Liza Minnelli.

Pakula was born in The Bronx, New York, to parents of Polish-Jewish descent, Jeanette (née Goldstein) and Paul Pakula. He was educated at The Hill School in Pottstown, Pennsylvania, and Yale University, where he majored in drama. From October 19, 1963, until 1971, Pakula was married to Actress Hope Lange. He was married to his second wife, Hannah Pakula (formerly Hannah Cohn Boorstin) from 1973 until his death in 1998.

In 1971, Pakula released the first installment of what would informally come to be known as his "paranoia trilogy". Klute, the story of a relationship between a private eye (played by Donald Sutherland) and a call girl (played by Jane Fonda, who won an Oscar for her performance), was a commercial and critical success. This was followed in 1974 by The Parallax View starring Warren Beatty, a labyrinthine post-Watergate thriller involving political assassinations. The film has been noted for its experimental use of hypnotic imagery in a celebrated film-within-a-film sequence in which the protagonist is inducted into the Parallax Corporation, whose main, albeit non-ostensible, enterprise is domestic terrorism.

Finally, in 1976, Pakula rounded out the "trilogy" with All the President's Men, based on the bestselling account of the Watergate scandal written by Bob Woodward and Carl Bernstein, who were played in the movie by Robert Redford and Dustin Hoffman, respectively. It was another commercial hit, considered by many critics and fans to be one of the best thrillers of the 1970s.

Pakula scored another hit in 1982 with Sophie's Choice, starring Meryl Streep. His screenplay, based on the novel by william Styron, was nominated for an Academy Award. Later commercial successes included Presumed Innocent, based on the bestselling novel by Scott Turow, and another political thriller, The Pelican Brief, an adaptation of John Grisham's bestseller. His final film was the crime drama thriller film The Devil's Own, where he reunited with Harrison Ford.

Pakula died on November 19, 1998, in a car accident on the Long Island Expressway in Melville, New York. He was 70 years old. A driver in front of him struck a metal pipe, which went through Pakula's windshield, struck him in the head, and caused him to swerve off the road and into a fence. He was killed instantly.