More powerful in every department with bags of pace up front despite the absence of top scorer Rob Duffy, Oxford could easily have doubled their score and did not look in danger of conceding a goal until four minutes from time.
Cambridge boss Jimmy Quinn switched to a new 3-5-2 formula in a bid to at least frustrate the unbeaten top of the table side, but it never looked convincing and was scrapped early in the second half.
Cambridge had an early half-chance when a cross from Jon Brady dropped to striker Marcus Richardson in front of goal, but he could only nudge the ball straight into the arms of goalkeeper Billy Turley.
So great was the gulf between the two old football league rivals however, that even if Cambridge had got off to such a shock flying start it would have been unlikely to save them from crashing their fifth home defeat of the season.
With Chris Hargreaves and Carl Pettefer completely dominating midfield, pulling all the strings throughout the match, Oxford were able to play the game they wanted at their own pace and had the players up front to turn some excellent moves into well taken goals.
They might have taken the lead as early as the eighth minute when Steve Basham burst into the box, but had the ball taken off his toe as he was about to shoot by a brilliant tackle from centre-back Michael Morrison.
It was only delaying the inevitable however and after Yemi Odubade and Pettefer went close, Oxford broke the deadlock in the 28th minute with a goal of embarrassing ease.
It was a nightmare moment on his debut by James Meredith, on loan from Derby County, when he tried to shield the ball near the right-hand touchline only to give it away to wing-back Eddie Anaclet.
He fed it into the centre where Basham might have gone for the shot himself, but instead played the ball wide in a penalty area mysteriously missing any defenders to Odubade who rammed the shot home from eight yards.
Not long afterwards it might have been 2-0 but Pettefer's blast from just outside the box whistled over the crossbar.
It was a sign of Cambridge's desperation just before the break when former Oxford player Rob Wolleaston went for goal from more than 30 yards and saw his shot disappear high over the bar into the crowing Oxford fans behind that goal.
Oxford somehow managed to increase their pace and pressure after the break, virtually wrapping things up as early as the 56th minute with a superbly worked goal.
The B squad of Andy Burgess, Basham and Rufus Brevett combining in a superb move which finished with the ball being lofted into the box where Hargreaves raced between the United centre-backs to aim a header down past helpless keeper Paul Crichton.
Goal number three seven minutes later was somewhat unfortunate for Cambridge in that it came from a dubious corner award, but nevertheless was again well taken by exciting youngster Odubade who took his tally to six for the season.
Barry Quinn's header did not appear to have touched any Cambridge player when it bounced away off the crossbar, but the corner was awarded and when Burgess flicked the ball in Chris Willmott headed the ball back from the far post for Odubade to finish ruthlessly from close range.
The only real question remaining in the game was whether Odubade was going to complete his hat trick, but he had a 78th minute shot brilliantly saved by the keeper and then let the ball run too wide when he broke through soon afterwards.
With four minutes remaining Cambridge substitute Liam Marum forced the only real save of the game from Turley with a header, but that snippet of goalmouth action was nowhere near enough to save Cambridge being booed from the field by their frustrated fans.