He was selected by the Pittsburgh Steelers in the first round of the 2006 NFL draft after playing college football for the Ohio State Buckeyes.

In 2009, Holmes was named the most valuable player (MVP) of Super Bowl XLIII as the Steelers beat the Arizona Cardinals.

Holmes attended Ohio State University where he was red shirted when the Buckeyes won the 2002 National Championship.

[1] Holmes left college a year early and was taken in the first round (25th overall) of the 2006 NFL draft by the defending Super Bowl XL champion Pittsburgh Steelers.

Early on in the Steelers' disappointing 2006 season, Holmes was criticized for his poor performance on special teams as a returner, a role in which he fumbled frequently.

Holmes saw his first score the following week in an overtime win against the Baltimore Ravens, finishing with 61 yards on 3 receptions for a touchdown.

He was forced to miss the following loss to the New York Giants, but was activated again for the Monday Night game against the Washington Redskins.

However, Holmes' still contributed big plays throughout the season, especially during the game versus the Cowboys where he caught a long pass that ignited a struggling Steelers offense.

[13][14] The trade came after Holmes' incident in a nightclub, coinciding with Ben Roethlisberger's own legal troubles, and the Steelers wanting to set an example for its other players.

[15] After serving a four-game suspension for violating the league's substance abuse policy, Holmes returned to practice on October 6, 2010.

[17] The very next week, on November 21, 2010, Holmes caught a game-winning touchdown from Mark Sanchez with 10 seconds left and the Jets went on to beat the Houston Texans 30–27.

In the 4th quarter of the final game of the 2011 season against the Miami Dolphins, Holmes appeared to get into an argument with Jets offensive tackle Wayne Hunter while the team was huddling.

[25] Holmes was lost for the remainder of the 2012 season after sustaining a severe Lisfranc foot injury in Week 4 against the San Francisco 49ers, and was eventually placed on injured reserve.

"[34] Holmes has acknowledged selling drugs on the street corner of his hometown of Belle Glade, Florida as a teenager; he says that his mother's influence and a desire to play professional football made him decide to stop.

Holmes was arrested for a second time on June 18, 2006, for domestic violence and assault in Columbus, Ohio.

[39][40] He released an apology after missing a game, stating that he wished to "focus all of [his] efforts on helping our team win on the field and achieve its ultimate goal.

Initially, Mills did not pursue charges, claiming Holmes and the police intimidated her into it, but the case has been reopened.

Subsequently, after a Twitter comment criticizing the nightclub incident, Holmes told the follower to "kill urself".

[43] On April 29, 2010, according to a report filed by authorities at Pittsburgh International Airport, a flight attendant told police that Holmes wouldn't turn off his iPod when requested and asked that officers speak to him.

Holmes got off the Colgan Air flight and spoke to the officers, who reminded him to comply with regulations, but did not charge the wide receiver with anything.