The Gay Meadow side stretched their unbeaten run to five matches and kept a second consecutive clean sheet, as Monday's 1-0 success at high-flying Leyton Orient was followed with an equally solid display.
Just as he did at Brisbane Road last Monday, Colin McMenamin netted with a first-half penalty, which was followed by a superb strike from midfield man Jamie Tolley as Town secured the points before the break.
In the previous match McMenamin netted with a third-minute penalty - and in this encounter it took him just five minutes longer, after he himself was sent crashing in the box by Oxford full-back Matt Robinson.
U's goalkeeper Billy Turley had saved penalties on his last two visits to Gay Meadow when playing for Rushden & Diamonds, but on this occasion was sent the wrong way by McMenamin's coolly taken kick.
Oxford hit back with worthwhile efforts from skipper Chris Hargreaves and Lee Bradbury, but were rocked again on 19 minutes when Tolley struck in fine style.
A cross from Shrewsbury striker Kelvin Langmead dropped into the penalty area, Tolley met it on the volley and his sweet strike into the bottom corner gave Turley no chance.
Before the break Chris Hackett forced a smart save from Shrewsbury's teenage goalkeeper Joe Hart, who impressed again in the second half with some confident handling as Oxford enjoyed a greater share of possession without threatening unduly to force their way back into the match.
Indeed, there was no way back for Brian Talbot's men after defender Barry Quinn was ordered off for a second bookable offence with a quarter of an hour remaining.