Strikers Lee Bradbury and Tommy Mooney grabbed a goal apiece three minutes into each half to give Oxford victory in front of the lowest league gate since they moved to the Kassam Stadium three years ago.
Oxford had three players who only just arrived in time for the kick off after being caught in a traffic jam on the M40.
They had been named on the team sheet handed in to the referee, so Oxford boss Graham Rix was a nervous man as the seconds ticked away.
Yet it was Shrewsbury who made a sluggish start with Bradbury scoring his first goal for his new club soon after the start.
Steve Basham won a vital header, Mooney played the ball through and Bradbury cleverly knocked the ball one side of the keeper and then went around the other before slotting home.
Oxford went onto dominate the game, completely out passing last season's promoted Conference play-off winners.
However, Shrewsbury had chances. Kevin Street and Luke Rodgers both blazed over.
Basham drove into the side netting for the U's and Shrews keeper Scott Howie was a busy man.
Rix brought on young midfielder Tom Winters for the second half and the 18-year-old midfielder made an instant impact.
From his left wing cross, Mooney headed low past Howie for his third goal of the season.
Rodgers broke clear in the second half but was denied by a fine save from Chris Tardif.
Jimmy Quinn's side missed a penalty in stoppage time after substitute Colin Cramb was fouled by Lee Molyneaux.
Cramb stepped up to take the spot kick himself but blasted it against the underside of the bar.
Shrewsbury players were accused of bad sportsman ship after a controversial incident in the second half when Ryan Lowe chose not to return the ball to goalkeeper Tardif after a stoppage following an injury to an Oxford player.
Instead, he kicked the ball into no-mans land between Oxford's defence and keeper and Rodgers tried to score.
Tardif saved and a linesman was flagging anyway. But Oxford players were angry that the ball had not been returned directly to their goalkeeper.