The loss at the Memorial Stadium left the Pilgrims just two points clear of the relegation zone and the board acted swiftly with an official statement being released less than two hours after the final whistle.
"The team's recent results have not been good enough and, with the club's Football League future paramount, the Argyle board felt a change was necessary now as we head into an important part of the season," it said.
"The owner and the board would like to thank Carl for all he has done for the club, as a player and a manager. The board will now seek promptly to appoint a new manager with significant experience of football management."
Fletcher played for the Pilgrims for two years before being named as caretaker player/manager in September 2011 following the departure of Peter Reid. He was given the job on a permanent basis two months later and helped keep the club in League Two last season but he oversaw just five wins out of 26 in 2012/13 before leaving Home Park.
Elsewhere, leaders Gillingham beat Southend 1-0 at Roots Hall with Chris Whelpdale's third-minute effort the only goal of the game.
Port Vale dropped off the top spot after a shock 2-0 defeat to Fleetwood, who moved up to sixth, while Rotherham moved up to third with a 2-1 win at Rochdale.
Cheltenham were pushed out of the top three after a 1-0 defeat at Oxford, and Bradford were held to a goalless draw at Morecambe.
Burton Albion suffered a 3-0 defeat at York City, but it was a better afternoon for Exeter, who beat Wycombe 1-0 despite having striker Jamie Cureton sent off.
Northampton beat Dagenham and Redbridge 3-1 at Sixfields, and they moved above Chesterfield, who lost 1-0 at Accrington.
Torquay went down 3-2 at home to bottom side AFC Wimbledon at Plainmoor, while Aldershot beat struggling Barnet 1-0 at Underhill.