James Constable crowned a man of the match display with the 16th minute winner to take his tally for the term to 11 goals.
Constable met right-back Damien Batt's pacy angled drive into the six yard box for the game's only goal.
Argyle keeper Jake Cole made a superb one-on-one stop to deny Oxford top scorer Tom Craddock following a poor backpass from Argyle right-back Durrell Berry in the 53rd minute and seconds later Constable hit the upright.
The closest Argyle came to a leveller was in the 63rd minute when forward Reuben Reid's sidefoot volley was headed off the line by Oxford skipper and central defender Jake Wright.
"I am delighted with the win," he said. "We have played okay in the last three or four weeks, just as well as when we won the four games on the bounce so it's a fine dividing line.
"We always knew it was going to be difficult coming to a team that's picked up quite considerably since John (Sheridan) has become the manager.
"As always you know it's a proper football club down here, with great supporters, a good place to come and play so I knew it would be a proper game so I am well happy with the players' response.
"I think we were bold in our selection, we went with four up top and wanted to take the game to the opposition and take the sting out of the game. I think we did that first and foremost.
"Obviously you want to make a quick start and getting our noses in front was good. It was a good finish for the goal. We had two or three other opportunities where we got clean through. They played a high line and we got down the sides with a little bit of success."