Azzarello's most notable work is the 100 issue long 100 Bullets with Eduardo Risso. He has also penned the ongoing original title "Loveless," a tale of post-Civil-War era corruption in the South, Deathblow series for Wildstorm and many DC Comics. He as also written for Marvel/Max.
Azzarello often collaborates with artists Eduardo Risso and Lee Bermejo.
On June 2, 2011, it was announced that he would be writing the new Wonder Woman ongoing series. He also stated that he intends to make Wonder Woman a horror comic book. He is also writing a new series Spaceman at Vertigo.
Azzarello is also one of the writers on the weekly The New 52: Futures End series that began in May 2014
He's married to Jill Thompson.