Pendergast had held the same job with the Arizona Cardinals from 2004-08, but was let go earlier this off-season, despite Arizona reaching Super Bowl XLIII.
Pendergast, 41, is a 14-year NFL coaching veteran and, in Kansas City, he rejoins former Cardinals' offensive coordinator Todd Haley, the Chiefs' new head coach.
Pendergast inherits a defense that gave up over 27 points per game in a dismal 2-14 2008-09 season.
"Clancy was instrumental in the Arizona Cardinals' run at the end of last season that led to our appearance in the Super Bowl," Haley said. "The fact that we have experience working together along with Clancy's previous experience working with (offensive coordinator) Gary Gibbs will be a big factor in our continuity as we move forward."