The reigning Romanian champions not only need three points but hope other results in group H go in their favour. Galatasaray take on Braga in the other fixture and also need a win to qualify for the knockout stages.
However, due to their inferior head-to-head record, CFR need a better result at Old Trafford to pip Galatasaray to second place. But they are guaranteed a spot in the UEFA Europa League, which means they will remain in Europe for the first time after Christmas.
Meanwhile, United boss Sir Alex Ferguson will rest several first-team players having secured qualification and keeping in mind the Manchester derby on Sunday.
Ferguson will be clearly worried about his hapless defence against Reading and demanded his back-line to improve ahead of the clash at the Etihad next Sunday.
United have several players injured in midfield with Shinji Kagawa, Nani, Antonio Valencia and Anderson sidelined for the clash against CFR and though defender Nemanja Vidic returned to full training Ferguson will rest him for now.
*Manchester United have conceded first in 14 out of 22 games in all competitions.
*This is United's 17th successive UEFA Champions League group stage campaign.
*Ryan Giggs has scored in a record 16th UEFA Champions League season and he is also the oldest scorer at 37 years and 289 days.
Manchester United (4-4-2): Lindegaard-Rafael, Smalling, Jones, Buttner-Cleverley, Giggs, Fletcher, Young-Welbeck, Hernandez.
CFR Cluj (4-4-2): Felgueiras-Pinto, Maftei, Cadu, Sepsi-Bastos, Camora, Muresan, Sougou-Pedro, Kapetanos.