Born Ralph Uriah Hunsecker in Broken Arrow, Oklahoma, Blane was the son of grocery store owners. He began his career as a radio singer for NBC in the 1930s before turning to Broadway, where he was featured in New Faces of 1936, Hooray for What!, and Louisiana Purchase. He contributed the lyrics and music to Best Foot Forward (1941) and Three Wishes for Jamie (1952).
With partner Hugh Martin, Blane penned many American standards for the stage and MGM musicals. The team's best-known songs include "The Boy (Girl) Next Door", "Have Yourself a Merry Little Christmas," and "The Trolley Song," all written for the 1944 film musical Meet Me in St. Louis. Although, during a December 21, 2006 NPR interview with Hugh Martin, he said Blane encouraged him to write 'Have Yourself a Merry Little Christmas', but did not have anything more to do with writing it. Facing the challenge of writing a song about a trolley, the duo visited a public library, and in a book found the caption "Clang, clang, clang went the trolley," which formed the nucleus for the lyrics of their song, which earned them their first Oscar nomination (their second was for "Pass That Peace Pipe," written in collaboration with Roger Edens for the 1947 film adaptation of Good News). Meet Me in St. Louis was adapted for a 1989 Broadway musical of the same name.