Shelley Long was born in Fort Wayne, Indiana. She entered Northwestern University as a drama major, but eventually dropped out to pursue a career in modeling and acting. While in Chicago, Long wrote, produced and co-hosted a local TV show called Sorting It Out. She was also a member of famed comedy troupe Second City.

Long moved to Hollywood in 1978 to pursue opportunities in film and television. She made her television debut on an episode of The Love Boat in 1978. Other early television appearances include Family, Trapper John MD, and M*A*S*H. She appeared in the Ringo Starr vehicle Caveman, and a turn as a prostitute in Night Shift, Ron Howard's film directorial debut, followed. Long became a household name when she was cast as Diane Chambers on the NBC sitcom Cheers. For four seasons, she played the snooty barmaid who had a tempestuous on-again-off-again relationship with caddish bar owner Sam Malone. In that time Long earned six Emmy Award nominations.

During her time on Cheers, Long maintained her film career, making Irreconcilable Differences, The Money Pit, Outrageous Fortune, and Hello Again. After leaving Cheers, Long put her focus on her film career, making occasional TV appearances on Murphy Brown, Boston Common, and Cheers spin-off Frasier. In recent years, Long has made appearances on 8 Simple Rules for Dating My Daughter, Joan of Arcadia, Boston Legal and Yes, Dear. In 1995 she recreated the role of Carol Brady in The Brady Bunch Movie, and went on to play the role in two sequels, A Very Brady Sequel and The Brady Bunch in the White House.

For 25 years Long was married to Bruce Tyson, but the couple divorced in 2004. They have one child together, a daughter.