Also Tuesday, the Padres told veteran reliever Matt Thornton that he will make the 25-man roster. They team also paid a retention bonus to right-hander Brandon Morrow, released outfielder Skip Schumaker and optioned right-hander Leonel Campos to Triple-A.
Humber, 33, threw a perfect game for the Chicago White Sox against Seattle in 2012. But his ERA ballooned to 7.90 a year later with Houston, and he hasn't pitched in the big leagues since.
Manager Andy Green said Humber is "ready to move on with his family."
The Padres faced a Tuesday deadline to tell Thornton, a lefty, whether he made the roster or release him. He signed a minor league deal earlier this month.
Green also announced that right-hander Jon Edwards will start the season on the disabled list with elbow pain.