[citation needed] Growing up in his father's town of San Severo in Apulia, he enrolled in 1974 at the Department of Arts, Music, and Entertainment of the University of Bologna.

Pazienza developed a personal body of work, alternating between playful comic cartooning—at times politically charged–and much more elaborate, dark, disturbing graphic novels, often dealing with drugs and wanton violence, with a scattering of black humor throughout.

In 1980, he created the character Zanardi and collaborated with the magazines Corto Maltese and Comic Art, while also producing movie and theatre posters, scene designs, record covers, and advertising.

Pompeo, his last graphic novel, which depicts the gradual downfall of a heroin addict (a largely autobiographical character) up to his eventual suicide, is generally considered his masterwork; the post-face to this work testifies that Pazienza tried to start a new life and, for a while, quit drugs.

[4] The nonprofit association Centro Fumetto Andrea Pazienza was created in his honour to help young cartoonists develop their skills.