Following encouraging medical tests, Holmes reported to the Chiefs' training camp in July 2007. However, the Chiefs did not include him on the roster at the start of the season, listing him on the non-football injury list instead. Michael Bennett was traded at mid-season, and Holmes returned to the Kansas City roster, beginning practice on October 17, 2007. Holmes then completed the comeback four days later, playing in the Chiefs regular season game against the Oakland Raiders, carrying the ball four times. He made his first start since October 30, 2005 against the San Diego Chargers and played in a home game on November 11, 2007 in a 27-11 loss to the Denver Broncos. Holmes had 20 rushes for 65 yards.