Aherne began performing on the Manchester comedy circuit as Mitzi Goldberg, lead singer of the comedy country and western act The Mitzi Goldberg Experience. She developed her Mrs Merton character with Frank Sidebottom for his show on Piccadilly Radio, where she worked as a receptionist. Aherne’s first TV appearances were a semi-regular spot on the Granada TV discussion show “Upfront” in 1990, as Mrs Merton. She made brief appearances in The Smell of Reeves and Mortimer (1993), alongside Steve Coogan and John Thomson in a Granada TV pilot entitled The Dead Good Show, then appeared in and wrote for the BBC comedy series The Fast Show between 1994 and 1997, and rose to prominence as the character Mrs Merton on the mock talk show, The Mrs Merton Show, in 1994.
Mrs Merton was a character created by Aherne who hosted her own chat show. Guests (real-life celebrities, not actors) found themselves on the receiving end of outrageous faux naïve questions. The series ran in various formats from 1994 to 1997, winning a BAFTA in 1995. The character was given a sitcom, Mrs Merton and Malcolm, which depicted her home life with her “mummy’s boy” son (played by co-writer Craig Cash). However, this aspect of Malcolm’s character was exaggerated to the point where many complained that the series made fun of people with learning difficulties. Mrs Merton and Malcolm lasted one series, and was only released on DVD in 2008.
Her most popular creation is the situation comedy The Royle Family, which she co-created and wrote with Cash, and directed in its third season. Aherne starred alongside Ricky Tomlinson and Sue Johnston, as their daughter Denise Royle. The show was a commercial and critical success, and ran for three seasons of six episodes as well as three one-offs.