He was born in Perugia, son of Filippo Vassalli, a famous lecturer and lawyer.

During World War II, Vassalli was imprisoned by Nazi forces in Rome and subjected to torture.

In 1987, Giovanni Goria named him Italian Minister of Justice; he was confirmed along with Ciriaco De Mita and Giulio Andreotti.

President Francesco Cossiga appointed him to the Constitutional Court of Italy on 4 February 1991 and was swore in nine days after.

In 2001, Prime Minister Silvio Berlusconi sought his advice over the European Arrest Warrant and Vassalli answered that it was a violation of the principles of natural justice.