In the season opener of the 2007 season, Bush and the Saints lost to the defending Super Bowl champion Indianapolis Colts 41–10. Bush was tied for a team-best 38 rushing yards on 12 carries. He also had seven yards on four receptions and a punt return for two yards in a disappointing opener for him and the Saints. Their next game was equally disappointing, as the Saints were beaten 31–14 by the Tampa Bay Buccaneers and Bush averaged 2.7 yards per carry and 27 yards from scrimmage – over a third of which came on one play. Bush scored two rushing touchdowns, both one-yard runs, in the Saints' Week 3 loss to the Tennessee Titans. In that game, Bush carried seven times for 15 yards while catching six passes for 20 yards. Bush missed the final four games of the 2007 season with a partially torn posterior cruciate ligament in his left knee. Bush finished the season with six total touchdowns and 581 yards rushing, averaging 3.6 yards per carry.