Oxford United 0-3 Arsenal: Nketiah at the double as Gunners set up Man City FA Cup tie
The Premier League leaders failed to register a shot on target in the first half at the Kassam Stadium on Monday after Mikel Arteta made seven changes to his starting line-up.
They demonstrated their superior quality after the break, though, Mohamed Elneny opening the scoring before in-form Nketiah struck twice in the space of six minutes.
Fabio Vieira provided two assists in a ruthless second-half display from Arsenal, but an injury sustained by Bukayo Saka will be a concern for Arteta ahead of their North London derby against Tottenham on Sunday.
League One side Oxford had not allowed the Gunners to settle in a frantic first half that was devoid of quality.
Arsenal wanted a penalty when Albert Sambi Lokonga's shot appeared to strike Elliott Moore's arm, before Nketiah poked over the crossbar from close range.
Matt Turner came out to deny striker Matty Taylor early in the second half after the Oxford striker got in behind a static Gunners defence.
Lewis Bate then blocked Saka's goal-bound strike after some neat footwork from the England winger in the penalty area as Arsenal showed more urgency.
Mikel Arteta introduced Granit Xhaka and Oleksandr Zinchenko just after the hour mark, and Elneny opened the scoring moments later, heading in Vieira's whipped free-kick from six yards out.
Nketiah raced onto an excellent pass from Vieira and rounded Edward McGinty to double the lead and finished clinically again after Gabriel Martinelli set him up to put Arsenal out of sight.