Manusky was the linebackers coach for the Washington Redskins and San Diego Chargers before he became the defensive coordinator of the San Francisco 49ers in 2007. Following the 2010 season, 49ers head coach Mike Singletary was fired by the team. Former Stanford University head coach Jim Harbaugh replaced Singletary. Harbaugh gave Manusky permission to interview with other teams, and Manusky quickly lined up interviews with three teams: the Chargers, Arizona Cardinals and Dallas Cowboys. Manusky ultimately accepted the defensive coordinator job with the Chargers, with whom he had previously worked as a linebackers coach. He was fired following the 2011 season on January 5, 2012.