The win sets up a blockbuster FA Cup fourth-round clash at Manchester City.
Mikel Arteta made seven changes from the recent goalless stalemate with Newcastle and the Premier League leaders were made to work for a 3-0 victory at the Kassam Stadium.
Neither side mustered a shot on target in an utterly-forgettable opening 45 minutes before Mohamed Elneny's first goal in 617 days broke the deadlock and a classy Eddie Nketiah brace wrapped up the win.
Bukayo Saka also limped off on a night where the scoreline ultimately flattered Arsenal, who now travel to their nearest title rivals City as a reward.
An even opening half-hour saw Arsenal dominate the ball without testing Edward McGinty in the Oxford goal.
While five of those coming into the visitors' side were fully-fledged internationals, there was a clear lack of the sort of cohesion which has seen them amass a five-point lead over Pep Guardiola's reigning champions at the Premier League summit.
Arsenal were denied a strong penalty shout as an Albert Sambi Lokonga drive was blocked by the flailing arm of Elliott Moore but, with no VAR in operation, referee David Coote was unmoved.
Not until 10 minutes after the interval did the capacity crowd witness a shot on target, Saka cutting inside before seeing his effort cleared off the line by Lewis Bate.
Arteta responded to the deadlock by introducing Granit Xhaka and Oleksandr Zinchenko from the bench - but it was another pair who combined for the opener.
Just moments after the changes and the 14-time FA Cup winners were ahead, Fabio Vieira - arguably the most ineffectual player on the pitch in the opening hour - providing a free-kick into the box which Elneny headed home with force.
Vieira was again on hand to lay on Arsenal's second, slipping in a fine through-ball which was collected by Nketiah, who showed his cool by rounding McGinty and tapping home.
Nketiah would double up for the evening with a deft finish from a Gabriel Martinelli pass, although he appeared offside, with a lack of VAR working in Arsenal's favour.
Saka had gone down injured moments earlier and limped around the side of the pitch to be replaced by Emile Smith Rowe - his fellow England international and Hale End academy product returning from a four-month injury lay-off.
He almost capped his return with a goal but saw an effort deflected inches wide of the post, although by that point the result was in hand.
Saka's knock will be the main concern for Arteta, who takes his side to face neighbours Tottenham on Sunday afternoon on the back of this hard-fought victory.