Holmes was a letterman in football, basketball, and track at Glades Central. In football, he helped lead his team to two state titles and a 12-1 record as a senior. Holmes attended Ohio State University where he was red-shirted when the Buckeyes won the 2002 National Championship. Holmes would eventually catch 245 passes for 2,295 yards and 25 touchdowns, while gaining 3,123 all-purpose yards. His 24 career receptions and 3,496 yards were ranked the fifth highest totals in school history at the time. His 25 touchdown catches ranked him 3rd in the NCAA. He was drafted by the Pittsburgh Steelers in the first round of the 2006 NFL Draft. In 2009, Holmes was named MVP of Super Bowl XLIII (43) as his team beat the Arizona Cardinals.