Jerome Kern was born in New York City. His parents, Fanny and Henry Kern, were both German Jews. They named him Jerome because they lived near Jerome Park, a favourite place of theirs (Jerome Park was named after Leonard Jerome, who was the father of Jennie Jerome, mother of British Prime Minister Winston Churchill). Fanny encouraged her son to take piano lessons. Henry was a merchandiser and sold pianos among other things. Although Henry wanted his son to go into business with him, Jerome insisted on staying with music.

He grew up on East 56th Street in Midtown Manhattan, where he attended public schools. He studied at the New York College of Music and then in Heidelberg, Germany. When he came back to New York, he started working as a rehearsal pianist, but it didn't take long for him to become a prominent and renowned composer. By 1915, he was represented in many Broadway shows. In 1920, he wrote "Look for the Silver Lining" for the musical Sally.

1925 was a major turning point in Kern's career, for he met Oscar Hammerstein II, with whom he would entertain a lifelong friendship and collaboration. Their first show (written together with Otto Harbach) was Sunny. Together, they produced next the famous Show Boat in 1927, which includes the well-known songs "Ol' Man River" and "Can't Help Lovin' Dat Man". Based on the book of the same name by Edna Ferber, "Showboat" was the first musical comedy to integrate plot and music into a cohesive story deviating from the usual musical revue of that era. (A 1946 revival would also try to integrate choreography into the show, in the manner of Rodgers and Hammerstein, as would the 1993 Harold Prince revival.) The musical Roberta (1933) gave us "Smoke Gets In Your Eyes" and starred Bob Hope.

In 1935, Jerome Kern moved to Hollywood and started working on music for films but continued working on Broadway productions, too. His last Broadway show was the rather unsuccessful Very Warm For May in 1939; the score included another Kern-Hammerstein classic, "All The Things You Are".

Kern's Hollywood career was successful indeed. For Swing Time (starring Ginger Rogers and Fred Astaire), he wrote "The Way You Look Tonight" (with lyrics by Dorothy Fields), which won the Academy Award in 1936 for the best song. Some other songs in the film include "A Fine Romance", "Pick Yourself Up", and "Never Gonna Dance". In 1941, he and Hammerstein wrote "The Last Time I Saw Paris", a homage to the French city just recently occupied by the Germans. The song was introduced in the movie Lady Be Good and won another Oscar for Best Song.

Although Kern generally wrote for musical theatre, the harmonic richness of his compositions lend themselves well to the jazz idiom, which typically emphasizes improvisation based on a harmonic structure — many have been adopted by jazz musicians and have become standard tunes.

Jerome Kern died from a heart attack at the age of 60 in New York.