Chargers head coach Norv Turner was thought to be on the hot seat after the team again failed to meet its lofty expectations, finishing in second place of the AFC West with an 8-8 record and missing the playoffs for the second straight year.
But Turner was retained after receiving strong support from several of San Diego's veteran players, a luxury Manusky apparently did not have.
Manusky had just finished his first season leading the defense, which ranked 22nd in the league in points allowed (23.6) and 16th in yards allowed (346.6) after leading the league in total defense in 2010 under Ron Rivera, who left to become the head coach of the Carolina Panthers.
Pagano now takes over after being a member of the Chargers' coaching staff for the past 10 years, most recently coaching a linebacking core that included last season's team-leader in sacks, Antwan Barnes (11).
"John has worked extremely hard and been very patient to get this opportunity," Turner said. "I'm excited about John's experience with this defense, his familiarity with our team and where we can go with his direction."