Segall was born in Chicago.
Harry Segall's writing career spans 1933 to 1959. Segall's plays, including Lost Horizons, appeared on Broadway in the mid-1930s. In 1933, Metro-Goldwyn-Mayer brought Segall to Hollywood as a contract writer. In 1936, he moved to RKO Pictures where he wrote and co-wrote screenplays for films such as The Outcasts of Poker Flat, based on a story by Bret Harte and Blind Alibi, starring Richard Dix. During this time, Paramount Pictures and Universal Studios also produced his screenplays. In 1941, Segall won an Academy Award for best original story for the film Here Comes Mr. Jordan, starring Robert Montgomery, based on Segall's play Heaven Can Wait. The play was later revived under the title Wonderful Journey, but the revival lasted only nine performances. A 1978 film version of Heaven Can Wait starred Warren Beatty, Julie Christie, and James Mason. The play was then filmed as Down to Earth, a vehicle for Chris Rock.
With the advent of television, Segall turned his writing talents to this medium, writing plots for TV series and Playhouse 90. He retired from screenwriting in 1959 and died November 25, 1975, in Woodland Hills, California. Segall was interred in Roosevelt Cemetery, in Gardena, California.