Shrewsbury fell to a 3-0 defeat against Oxford at the Kassam Stadium.
Fin Stevens and Ciaron Brown scored either side of half-time to win the game for Liam Manning's side - with Greg Leigh grabbing a third in stoppage time.
Town had to play the majority of the second half with 10 men after Joe Anderson picked up a second yellow card for a foul on Stevens.
Oxford’s win saw them increase the gap between third-place Bolton and would've seen them go top but for Portsmouth's 99th-minute winner on the night.
Boss Matt Taylor opted to make four changes from the team that put in an impressive display against Charlton when naming his starting line-up.
Sticking with a 3-5-2 formation, Elliott Bennett and Joe Anderson came into the side at wing-back in a move that saw Carl Winchester move into central midfield.
He was joined in the middle of the park by Nohan Kenneh and Tom Bayliss with Ryan Bowman and Kieran Phillips the front two.
Oxford lined up in a 4-2-3-1 formation with Billy Bodin operating in the number 10 role behind Marcus McGuane. Greig Leigh and Ruben Rodrigues were the widemen.
It was the home side who created the first chance of the game with a ball over the top looking to have got Mark Harris through on goal.
Morgan Feeney, though, did well to read the danger with the defender using his strength to muscle the striker off the ball.
Town responded with Bayliss sending in a cross that a defender did well to clear ahead of Bowman. Bayliss then saw an effort from 20 yards claimed by the keeper.
But in the 17th minute, the hosts got themselves ahead when Greg Leigh’s cross went through Marko Marosi - with Stevens on hand to tap in from close range.
Town created two chances as they searched for a quick reply.
First, Bayliss sent in a cross which Chey Dunkley fired over the bar.
Kieran Phillips then showed his pace to hit the byline before standing up a cross that a defender cleared ahead of Bowman.
Oxford should have doubled their lead shortly before the break in a move that started from a Town corner.
The U's countered at speed with Cameron Brannagan playing Harris in one-on-one only for the striker to put his effort wide of the post.
Town's hopes of getting back into the game were dealt a major blow just before the hour mark when Anderson picked up a second yellow card for a late challenge on Stevens.
Then from the resultant free-kick, Brown fired in from close range to double the hosts' lead.
Taylor responded by making a quadruple change with Brandon Fleming, Taylor Perry, Dan Udoh and Max Mata all entering the fray - with Salop lining up in a 4-3-2 system.
But there was no way back for Taylor's side with Oxford going on to grab a third late on when Marosi lost possession and Leigh curled in a brilliant strike from a tight angle.
Oxford: James Beadle, Sam Long, Ciaron Brown, Elliott Moore, Cameron Brannagan, Billy Bodin (Tyler Goodrham 45’), Fin Stevens, Mark Harris (Gatlin O’Donkor 73’), Ruben Rodrigues (Josh McEachcran 67’), Greg Leigh, Marcus McGuane
Unused Substitutes: Simon Eastwood, Jordan Thorniley, Josh Murphy, Stan Mills
Shrewsbury: Marko Marosi, Joe Anderson, Morgan Feeney, Chey Dunkley, Tom Flanagan, Carl Winchester (Taylor Perry 61’), Elliott Bennett (Brandon Fleming 61’), Nohan Kenneh (Tunmise Sobowale (84’), Tom Bayliss, Ryan Bowman (Dan Udoh 61’), Kieran Phillips (Max Mata 61’)
Unused Substitutes: Harry Burgoyne, Mal Benning
Referee: Charles Breakspear