On June 26, 2008, Mayo was selected 3rd overall in the 2008 NBA draft by the Timberwolves. Later that day, he was traded to the Memphis Grizzlies, along with Marko Jarić, Antoine Walker, and Greg Buckner, swapping them for the 5th overall pick Kevin Love, Mike Miller, Brian Cardinal, and Jason Collins. Mayo was a part of the Select Team that helped get the U.S. national team ready for the 2008 Summer Olympics in Beijing. In his NBA Summer League debut, Mayo had 15 points to lead the Grizzlies to an 88–75 win over the New Orleans Hornets. During his rookie season, Mayo scored 30 or more points seven times. Mayo was the runner-up for the 2008–09 NBA Rookie of the Year Award, finishing second behind Chicago Bulls point guard Derrick Rose.