He played college football for Ole Miss Rebels, and was selected by the Pittsburgh Steelers in the third round of the 2009 NFL draft with the 84th overall pick.

Throughout his career, Wallace was known for his speed after finishing with a time of 4.33-seconds in the 40-yard dash at the NFL Scouting Combine.

He attended O. Perry Walker High School, where he played football on both offense and defense and his teammates included future New Orleans Saints cornerback Keenan Lewis.

He received first-team All-State honors as a wide receiver, and earned league and district MVP honors as well as All-League, All-Metro, All-West Bank and All-West Bank MVP following his senior season.

He also returned four punts and four kickoffs for touchdowns, giving him 27 for the season and 162 points, with seven more scores called back due to penalties.

[4] Also a standout track & field athlete in high school, Wallace earned All-State honors in the 100-meter dash as a senior.

Walker 4 × 100 meter relay squad at the 2004 State Outdoor Championships, helping them earn a fourth-place finish with a school-record time of 41.81 seconds.

SuperPrep named him the 17th-ranked college prospect in the state of Louisiana and selected him to its 2004 Southwest Team.

[16][17][18] At the 2009 NFL Scouting Combine, Wallace finished second overall in the 40-yard dash with an official 4.33-second time.

[23] In Pittsburgh he was reunited with former high school teammate Keenan Lewis, whom the Steelers selected just twelve picks after Wallace.

Wallace achieved his first 100-yard receiving game against the Cincinnati Bengals in Week 3 of the 2009 season; he had 7 receptions for 102 yards.

[24] On December 20, Wallace caught a game winning pass while falling out of bounds as time expired to defeat the Green Bay Packers, 37–36.

[29][30] Following his promising rookie season and Santonio Holmes' trade to the New York Jets, Wallace was moved up the depth chart in 2010 to the #2 receiver spot behind Hines Ward.

In 2010, Wallace had a standout second season with the Steelers, establishing himself as one of the NFL's elite wideouts with 1,257 yards receiving (third most in the AFC) and 10 touchdowns.

[29] During Super Bowl XLV against the Green Bay Packers, Wallace had nine catches for 89 yards and a touchdown.

[37][38][39] Against the Arizona Cardinals in Week 7, he and Roethlisberger connected for a 95-yard touchdown reception, becoming the longest in Steelers history.

[51] On March 12, 2013, Wallace was reportedly signed by the Miami Dolphins in a five-year deal worth $60 million.

[52][53] Wallace's father revealed that, despite that the Minnesota Vikings offered a bigger contract, Mike decided to move his home to a warmer Miami.

[65] In Week 9, against his former team the Pittsburgh Steelers, Wallace caught a 95-yard touchdown from Joe Flacco in a 21–14 victory.