Büttner arrived at Old Trafford from Vitesse Arnhem last week and is expected to provide valuable cover for Patrice Evra at left-back this season.
He starts in that position tonight for the U21s alongside Jonny Evans, who makes his return to action in the centre of defence following a summer spent recovering from an ankle operation.
Evans hasn't played a minute of football – either during pre-season or competitively – since the final day of the 2011/12 season, although his status as an unused substitute in Saturday's 3-2 win against Fulham suggests he's very close to full fitness. He'll aim to prove to Sir Alex Ferguson he's ready for a first-team start at Southampton this weekend by coming through tonight's match unscathed.
There's also another Under-21s appearance for midfielder Darren Fletcher, who played 90 minutes in the team's opening fixture, a 1-0 win away at Stoke City.
Tottenham, meanwhile, have included highly-rated defender Steven Caulker and striker Harry Kane in their squad.
The match will be broadcast exclusively live on MUTV and a full match report will appear on ManUtd.com afterwards.