Fresu was born in Berchidda, Sardinia. He picked up the trumpet at the age of 11, and played in the band Bernardo de Muro in his home town Berchidda. Fresu graduated from the Conservatory of Cagliari in 1984, in trumpet studies under Enzo Morandini, and attended the University of Musical and performing arts in Bologna.
Fresu has taught at the Siena Jazz National Seminars, as well as jazz university courses in Terni, and is the director of Nuoro Jazz Seminars in Nuoro, Italy.
Fresu composes music for theatre, poem, dance, radio, television, and film.
In 2007, Fresu recorded and toured with Carla Bley's quartet, The Lost Chords.
Award winning group Paolo Fresu Quintet has been invited to perform in SiriFort Auditorium, New Delhi. The event has been organised to celebrate 10 years of Italian Culture Centre in New Delhi.