Anderson served as Frye's backup for the Cleveland Browns in 2006 season. He made his NFL debut against the Denver Broncos at Cleveland Browns Stadium, on October 22, taking one snap after Frye was briefly shaken up. His second NFL appearance was more noteworthy. After Frye injured his wrist during the first half of Cleveland's December 3 game against the Kansas City Chiefs, Anderson played the entire second half. He threw his first two NFL touchdowns in that game, connecting with tight end Steve Heiden twice in the fourth quarter. Anderson scrambled for 33 yards in overtime, moving the ball from the Kansas City 45-yard line to the 12-yard line, after which the Browns were in field goal range. His play was instrumental in leading the Browns back from a 28–14 deficit to a 31–28 overtime victory.