Weston's first role was in a 1975 episode of Thriller, and parts in Raffles, The Sweeney, The Professionals, Agony, Shoestring and Bless Me, Father soon followed. She also appeared in the video for the 1984 Ultravox hit single Dancing with Tears in My Eyes. Since the late 1980s, she has appeared in The New Statesman, Boon, A Bit of a Do, About Face, Nightingales, Jonathan Creek, Casualty, Emmerdale, My Family, New Tricks and a main role in the 2000 sitcom Pay and Display.
Diana Weston had a long relationship with the actor Robert Lindsay, and they had one daughter, Sydney (born 1988), who has also made television appearances. She and Lindsay separated after he started a relationship with actress/presenter Rose Marie Ford, although she continued to work with him on occasion.
However it is for the role of Caroline in sitcom The Upper Hand that she is best remembered, starring alongside Joe McGann and Honor Blackman, with the show being a huge success for ITV from 1990-1996.