The Gunners picked up a massive 2-0 win over top-four rivals Chelsea last weekend to keep their Premier League campaign alive, but now focus turns to the domestic cup.
Arsenal have won both previous home fixtures against United in this competition - 5-0 in January 1937 and 2-1 in February 1988 - but they have their work cut out stopping their opponents' momentum, which has seen them win seven matches on the spin.
Ahead of this latest high-profile fixture between the Premier League giants, Sports Mole looks at how Unai Emery's side could line up.
Arsenal have six days' rest between the Chelsea and United matches, so Emery is expected to name a far stronger side than the one that started the 3-0 win over Blackpool in round three.
Mkhitaryan is likely to miss out against his former club, despite returning to training this week, while Bellerin is the latest long-term absentee for Arsenal after picking up a serious knee injury against Chelsea.
Emery must decide whether to go with two out-and-out strikers, as was the case against Chelsea, or stick with one of Pierre-Emerick Aubameyang or Alexandre Lacazette. Joe Willock and Alex Iwobi should start either side, meanwhile, after impressing in the last round.
There is also a decision to be made over Mesut Ozil's inclusion, as the German playmaker was back in the matchday squad last weekend but has not played a single minute since the draw with Brighton & Hove Albion on Boxing Day.