Ole Gunnar Solskjaer will take charge of United for the first time and he faces a tough task to turn their season around.
United head into the weekend sixth in the table, 11 points adrift of fourth-placed Chelsea.
The Bluebirds are currently 16th in the standings, just two points above the relegation zone.
The two sides last met in the top flight during the 2013/14 season, with United taking four points from the two games.
Cardiff are priced at 19/4 to win the game, with United available at 3/5 and the draw on offer at 3/1.
Confirmed starting line-ups:
— Cardiff City FC (@CardiffCityFC) December 22, 2018
— Manchester United (@ManUtd) December 22, 2018