Born in New Orleans, Rose moved to Hollywood where he found a job working as a comedy sketch writer with George Carlin. Among other assignments, he wrote for the Mort Sahl TV show， Eventually, Rose transitioned to songwriting.

David Bowie covered the song "Fill Your Heart," written by Biff Rose and Paul Williams, on his album Hunky Dory (1971), making it Rose's most well known composition. It was originally released by Tiny Tim as the B-side to his 1968 hit single "Tiptoe through the Tulips， Rose was instrumental in giving Williams his start in the music business; Williams wrote in the liner notes of his greatest hits package Evergreens – The Best of the A&M Years (2004) that Rose was his first songwriting collaborator and ultimately, his connection to A&M Records, having gotten Williams a meeting with publisher Chuck Kaye， Rose and Williams also collaborated on "I'll Walk Away", from Rose's third eponymous record (Rose composed music and Williams wrote lyrics)，