Riley became a popular television performer in the sketch shows Fast Forward, its successor Full Frontal, Big Girl's Blouse and Something Stupid. In the latter she was also a producer and writer. On Fast Forward, Gina Riley sent-up such singers as Paula Abdul, Bette Midler and Dannii Minogue as well as Australian personalities Kerri-Anne Kennerly and Jacki MacDonald. She later appeared in The Games, a spoof behind-the-scenes look at the organizing committee of the Sydney Olympics.

Recently she has enjoyed great success as Kim Craig and Trude in Kath & Kim, written, produced and created by Riley and her long-time writing partner and friend Jane Turner. Riley also works frequently with Magda Szubanski.

In contrast to the rest of her cast (such as Glenn Robbins, Peter Rowsthorn and Magda Szubanski), Riley makes relatively few public appearances as herself. Most of the time she appears in character as Kim, with Jane Turner. One notable exception was on Enough Rope with Andrew Denton, where she and Turner both appeared as themselves.

Riley has also had some roles in musical theatre. One notable role was as the baker's wife in a 1998 Australian Melbourne Theatre Company production of Into the Woods. She also appeared on stage as Janet in The New Rocky Horror Show; she is included on the cast album. In 2009, she played the part of Matron "Mama" Morton in a production of Chicago.