The Sky Blues lost at home for the first time this season after a below par performance, with Plymouth substitute Cherno Samba grabbing a late goal.
Micky Adams made three changes, bringing Stern John back in for the injured Leon Mckenzie, Andrew Whing for the suspended David McNamee and Colin Cameron for Michael Doyle.
The Irishman dropped to the bench, indicating that the City boss either felt he needed a rest or that he required more experience in the engine room.
In a lively start to the game City skipper Stephen Hughes got the first shot on goal in the second minute after good work from Jay Tabb, but his 20-yard drive was straight at Plymouth keeper Luke McCormick.
The Sky Blues continued to exert all the pressure and Stern John was inches away from connecting with a fine Chris Birchall cross before Tony Capaldi nearly turned the ball into his own net.
From that Plymouth launched a rapid counter attack but Reuben Reid could only find the side netting with the goal at his mercy after he was played through on goal by David Norris.
Argyle then enjoyed a prolonged spell of pressure, demonstrating some excellent passing moves and showing why they have only been beaten once on their travels this season.
Andy Marshall had to be alert to a Nick Chadwick shot after the Plymouth striker had forced an uncharacteristic error from Robert Page.
After a period where they had not really been at the races, City finished the half strongly and McCormick produced a fine save from a stinging Stern John effort to keep the scoreline goalless at the break.
Plymouth once again showed their attacking intent from the restart with Akos Buzsaky posing their main threat going forward. The Hungarian left midfielder - who was once signed by Jose Mourinho at Porto - was a constant menace and he shot just over from 25 yards with 49 minutes on the clock.
In the 65th minute, City made their first switch with Dele Adebola replacing Chris Birchall as the Sky Blues switched to a 4-3-3 formation, looking to put the Plymouth defence under more pressure.
Soon after, Don Hutchison replaced Jay Tabb, while Ian Holloway introduced Cherno Samba for Reuben Reid and the substitute grabbed the winning goal for the Pilgrims in the 82nd minute, planting a firm downward header into the back of the net from a left wing cross, leaving Andy Marshall with little chance.
City could have few complaints, having created no chances in the second half, whereas Plymouth looked bright throughout the 90 minutes and regularly had the home side on the back foot.
Coventry: Marshall; Whing; Hall; Page; Ward; Hughes; Kyle; Birchall (Adebola 65); John; Tabb (Hutchison 73); Cameron. Subs (not used): Doyle; Heath; Thornton
Plymouth: McCormick; Nalis; Norris; Buzsaky (Aljofree 78); Chadwick (Summerfield 85); Doumbe; Capaldi; Wotton; Seip; Connolly; Reid (Samba 74). Subs (not used): Larrieu; Sawyer
Referee: Mr M Halsey
Attendance: 19,545 (1,186)
