In 1960 Sandrelli won the Miss Cinema Viareggio beauty contest, then she was the cover girl of the magazine Le Ore and had the first opportunities to make films, appearing, among others, in Luciano Salce's Il federale. Her film career was launched by Pietro Germi with Divorce, Italian Style (1961); later she worked three more times with Germi, in Seduced and Abandoned (1963), L'immorale (1967) and Alfredo, Alfredo (1970).
Sandrelli became in a short time a protagonist of the commedia all'italiana, appearing, among others, in Antonio Pietrangeli's Io la conoscevo bene, Mario Monicelli's Brancaleone alle crociate and Ettore Scola's C'eravamo tanto amati. She also starred in several Bernardo Bertolucci's drama films, including The Conformist (1970) and 1900 (1976), and in several French productions.
In 1980 she won the Nastro d'Argento for Best Supporting Actress thanks to her performance in Ettore Scola's La terrazza. In 1983 she relaunched her career with the Tinto Brass' erotic film The Key; following the success of the film she then played a brief series of erotic films of good success.
On 10 September 2005 she received the Golden Lion for Lifetime Achievement at the 62nd Venice International Film Festival. On 11 May 2012 she received the title of Chevalier (Knight) of the Ordre des Arts et des Lettres.
She had a brother, Sergio, seven years older, who had a successful music career and died in 2013.