On April 24, 2010, Webb was drafted by the Minnesota Vikings, 199th overall in the sixth round of the 2010 NFL Draft. He was originally drafted as a quarterback/wide receiver prospect, but then head coach Brad Childress announced that Webb would exclusively play quarterback for the Vikings.
Webb's National Football League (NFL) debut was against the Buffalo Bills on December 5, 2010. He took the opening kickoff – becoming the first Vikings quarterback to return a kickoff – before leaving the game with a hamstring injury.
Webb made his professional debut at quarterback on December 13, 2010 against the New York Giants. He completed two-of-five attempts for eight yards and also had a 16-yard run.
Webb rushed for his first professional touchdown as quarterback on December 20, 2010, against the Chicago Bears in Minnesota. Filling in for an injured Brett Favre, he completed 15-of-26 passes for 129 yards, with two interceptions; he also had six rushing attempts for 38 yards and a touchdown.
On December 28, 2010, Webb made his first career start, against the Philadelphia Eagles. Scoring one rushing touchdown and throwing for 195 yards, he was 17-of-26 with no interceptions. Initially projected to lose by two touchdowns, the Vikings pulled off an upset win, 24–14. In the regular season finale against the Detroit Lions, he finished with 145 passing yards and an interception in the 20–13 loss.