During his university studies of philosophy in Messina, Amelio got interested in cinema, writing as film critic for a local magazine.

Two years later he directed the mystery La morte al lavoro, which won prizes at Locarno and Hyères festivals.

In 1982 he debuted for cinema proper with Blow to the Heart (Colpire al cuore), about Italian terrorism, presented at the Venice Film Festival.

In 1987 Amelio released I ragazzi di via Panisperna, about the lives of 1930 Italian physicists such as Enrico Fermi and Edoardo Amaldi, which won the award for best screenplay at the Bari Film Festival.

Amelio gained another Silver Ribbon as best director for The Keys to the House (Le chiavi di casa), inspired to a novel by Giuseppe Pontiggia, of 2004.