Born in Povegliano Veronese, Del Santo started her career as "valletta" in the 1975 edition of Festivalbar. In the late-1970s she obtained her first film roles, mainly in sexy comedy films, and in 1980 she entered the Miss Universe competition. In the early-1980s Del Santo became popular thanks to her participation in successful TV shows such as Antonio Ricci's Drive In and Renzo Arbore's Tagli, ritagli e frattaglie.
Del Santo was a focus of gossip columns, mainly for her relationship with Eric Clapton (who dedicated the song "Lady of Verona" to her) and for the death of their son, Conor. While he was still married to Pattie Boyd, Clapton fathered Conor who was born on 21 August 1986. Conor died in 1991, at the age of four and a half, when he fell out of an open bedroom window on the 53rd floor of a Manhattan apartment building. The death of their son was the inspiration for Clapton's songs, "Tears in Heaven" and "Circus Left Town".
In recent years she has taken part in several Italian reality shows, winning the third season of L'isola dei famosi. In 2006 she wrote an autobiography, Piacere è una sfida.
