Wendy Harmer gained a diploma in vocational writing at Gordon Institute of Technology, Geelong, and then worked as a journalist. She eventually gave up journalism and became a writer and comedian. She wrote for, and performed in, a number of ABC TV programs, such as The Gillies Report and The Big Gig, and she had her own late night chat show, In Harmer's Way (1990), and worked for a Sydney radio station. During the boom in Australian comedy in the 1980s, she became one of Australia's top female comedians. She was the first woman to host a TV comedy show in Australia.
Harmer has stated that one of the factors leading to her career in stand-up comedy was her experience growing up with a double cleft lip and palate (which were surgically corrected when she was fifteen, in an operation that required her mouth to be sewn closed for three months).
Harmer was appointed a member of the board of the Playbox Theatre in 1986. She has conducted comedy writers workshops at several institutions and has been involved in organising and performing at comedy festivals in Australia and overseas.
Harmer has also found success as a novelist. She has written books for children, young adults, and adults. Her 'Pearlie' series has been translated into ten languages, and has also been made into an animated television program.