Paul Hayes grabbed the only goal of the game after 36 minutes, nodding home from close range after Aaron Pierre powerfully headed Joe Jacobson's corner back towards goal.
It was a fifth game unbeaten for Wycombe and a third successive win at Home Park, which is proving to be a lucky stomping ground for Gareth Ainsworth's men.
Ainsworth said: "There was not much in the game. I thought we limited Plymouth's chances on our goal.
"We have taken our chance with the corner, and maybe on the break we might have troubled them again. I was really pleased the way we defended and saw the game out."
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