Mezzano started his career at hometown club Torino, and joined Internazionale in 1997. Despite being contract for four seasons with the Nerazzurri, he only made four appearances with the club and was mostly sent on loan to several other teams instead. He returned to Torino in 2001, spending four seasons with the club before ending his career after spells with Bologna, Treviso, Triestina and Arezzo. He retired in 2010, aged 33.
He has been played 71 Serie A games, which he made his debut against A.S. Roma, on 25 February 1996.