Rosenthal was born in Cheetham Hill, Manchester, and after studying English Literature at Sheffield University, carried out his National Service in the Royal Navy. He worked briefly in advertising before joining Granada Television. He earned his first television credit with them in 1961, assigned as a writer of episode 31 of Britain's longest-running soap opera, Coronation Street. He became a regular writer for the series and began writing for other series as well. During the 1960s, he contributed material for various television comedy shows including the satirical That Was The Week That Was. At Granada Television, he wrote a spin off series from Coronation Street for the character, Leonard Swindley, played by Arthur Lowe called Pardon the Expression and created two comedy series The Dustbinmen and The Lovers starring Richard Beckinsale and Paula Wilcox. In 1976 he also wrote a TV drama for ITV, called Ready When You Are, Mr McGill, which was later remade in 2003.

Rosenthal won three BAFTA awards for Bar Mitzvah Boy (about a Jewish boy's Bar Mitzvah), The Evacuees (based in his own war-time evacuation) and Spend, Spend, Spend (about the football pools winner, Viv Nicholson, directed by John Goldschmidt). He also wrote The Knowledge, a film about London taxi-drivers which has become a classic for cabbies-in-training. He created London's Burning as a one-off drama in 1986, and this later developed into a long-running TV drama. Rosenthal adapted the novel "The Devil's Lieutenant" for director John Goldschmidt as a mini-series for Channel 4 and ZDF, and wrote the screenplay of "Captain Jack" (based on a true story) for producer John Goldschmidt.

In 1983, Rosenthal co-wrote the film Yentl with Barbra Streisand. He also did uncredited work on the screenplay of Chicken Run.

Rosenthal also wrote the book for the musical version of Bar Mitzvah Boy, with music by Jule Styne.

He married actress Maureen Lipman in 1974, and they have two grown-up children, writers Amy Rosenthal and Adam Rosenthal. Jack Rosenthal was a Manchester United fan all his life.

Rosenthal was awarded the CBE in 1994.

He died in Barnet, London, aged 72, on 29 May 2004, following a long battle against multiple myeloma, a form of cancer.

His autobiography, By Jack Rosenthal was published posthumously and a four-part adaptation by his daughter, titled Jack Rosenthal's Last Act was broadcast to great acclaim on BBC Radio 4 in July 2006 starring Maureen Lipman as herself and Stephen Mangan as Jack Rosenthal.