The Reds have disposed of Arsenal and Leicester City to reach this stage and the defence of the trophy continues with a third successive top-flight opponent.
It is the third time we've faced the Cottagers this term, after winning both the league games 1-0. Debutant Joshua Zirkzee came off the bench to score on the opening day, while Lisandro Martinez's deflected strike earned all three points at Craven Cottage in January.
The 16:30 GMT kick-off will feature semi-automated offside technology for the first time at Old Trafford, in addition to VAR being reintroduced from this round onwards.