He has written lyrics for almost thirty years, most notably in partnership with Glenn Tilbrook. The two were primary members in Squeeze and Difford & Tilbrook Some of their best-known songs are "Tempted", "Pulling Mussels (From the Shell)", "Black Coffee In Bed", "Cool For Cats", "Up The Junction" and "Annie Get Your Gun".

In 2004 Lisa Stansfield released the Trevor Horn produced single "If i Hadn't got you" co written by Difford and Chris Braide which became a hit in europe.

Recently, Difford signed to Luna Records and released an album and DVD, South East Side Story, on 7 August 2006.