Cryer is the son of Gretchen Cryer (née Kiger), a playwright, songwriter, actress, and singer, and David Cryer, an actor, singer, and producer.He has two sisters, Robin and Shelley. Cryer attended Stagedoor Manor Performing Arts Training Center for several summers as a teenager and is a 1983 graduate of the Bronx High School of Science.

At age nineteen Cryer first appeared in the in 1984 romantic comedy film No Small Affair, having the lead role as Charles Cummings. He then had some small roles in films and made for television movies but his real breakthrough came when he was cast to portray Phil "Duckie" Dale in the John Hughes film Pretty in Pink. Thanks to this Cryer slowly became more famous, in 1987 he even got to portray Read more...

He married British-born actress Sarah Trigger in 1999, by whom he has a son, Charlie Austin, but the pair divorced in 2004. In June 2007, he married entertainment reporter Lisa Joyner. Cryer is good friends with Paget Brewster.