United have failed to win any of their last four matches in the competition, while Fulham are stuck in last place and have just two wins this season.
OddsShark lists Fulham as 15-2 shots to pull off an upset at Old Trafford. United come in at 33-100, and a draw carries odds of 9-2.
Both teams carry poor form into this fixture but had encouraging results in midweek. The Red Devils played out a sloppy 2-2 draw against Arsenal, twice overcoming a deficit, and Fulham earned a point at home against Leicester City.
The Cottagers have improved lately, per Bleacher Report's Sam Tighe:
With four points from their last three matches they've done better than United in that span, who have three. And while there were some positives to take away from the draw against Arsenal, there is still work to be done for the Red Devils.
The gap to league-leaders and rivals Manchester City is already a massive 18 points, and United sit in eighth place, eight points behind Arsenal and the final UEFA Champions League qualifying space.
Fulham provide the Red Devils with an opportunity to make a statement, and if they don't, Bleacher Report's Rob Blanchette thinks it will be the end of Jose Mourinho:
This will be the first meeting of the two teams since 2014, when the Cottagers snapped a losing streak with a surprise 2-2 draw at Old Trafford. Fulham were bottom of the table at the time, and Darren Bent found an equaliser in injury time.
The Red Devils will hope to avoid a similar scenario on Saturday. Fulham have conceded a league-worst 36 goals already, so Mourinho's troops should take the fight straight to them, applying pressure early and often.
Prediction: United 2-0 Fulham