Brown announced on January 7, 2010 that he would forgo his senior season and enter the 2010 NFL Draft. He was selected by the Steelers 195th overall in the 6th round.
On September 19 against the Tennessee Titans, Brown made his regular season debut and had 128 yards on 3 returns (2 kickoffs, 1 punt), including an 89 yard touchdown from a reverse on the first play of the game. In the AFC Divisional Playoffs against the Baltimore Ravens, Brown caught a 58 yard pass on 3rd & 19 from quarterback Ben Roethlisberger to set up the game-winning touchdown. The following week in the AFC Championship against the New York Jets, at the two-minute warning, Brown caught a 14 yard pass on 3rd & 6, sealing the victory for Pittsburgh as they advanced to Super Bowl XLV. On October 30, 2011, Brown caught his first pro touchdown on a seven-yard pass from quarterback Ben Roethlisberger. On December 4, 2011, Brown returned his first punt return for a touchdown against the Bengals, and was also named AFC Special Teams Player of the Week.
In 2011, Brown became the first player in NFL history to have more than 1,000 yards receiving and returning in the same year.