Monroe was selected with the 7th overall pick in the 2010 NBA Draft by the Detroit Pistons. On July 6, 2010, Monroe signed with the Pistons. Monroe will be the last Pistons player to wear the #10 jersey, as the Pistons retired the number for Dennis Rodman at halftime of a game against the Bulls on April 1, 2011.
Monroe made his NBA regular season debut on October 30, 2010 against the Chicago Bulls. He came off the bench to score 2 points and 3 rebounds in 7 minutes. After coming off the bench for the first month of the season, Monroe made his first career start on December 10, 2010 against the Minnesota Timberwolves. In this game, Monroe recorded eight points, fifteen rebounds and a block in 35 minutes of action. Despite a slow start to the season, Monroe's production increased in 2011 as he became a solid scorer and rebounder for the rebuilding Pistons. On February 23, 2011 against the Indiana Pacers, Monroe had his best game thus far with 27 points and 12 rebounds on 11–17 shooting.
On May 4, 2011, Greg Monroe placed 6th in NBA Rookie of the Year voting totals, finishing closely behind Gary Neal of San Antonio.