The Argentine centre-back, sidelined for 10 months following an ACL injury sustained against Palace in February, has now been given full medical clearance.
Rúben Amorim's side head into the weekend off the back of a 1-0 defeat to Everton, a result that extended their winless run to three matches.
Despite facing 10 men for most of the contest, United lacked a cutting edge and saw their five-game unbeaten streak halted.
A challenging trip to Selhurst Park now awaits. United have failed to win their last five visits to the south London ground, while Palace have lost only once at home this season.
Martínez's return therefore provides much-needed stability as the club chases a return to European competition after last season's disastrous 15th-place finish.
Speaking to MUTV, Amorim made it clear the defender is available for selection:
"If he is on the bench, he is ready. Of course, we need to control his minutes but, if he is on the bench, he is ready to play."
While Martínez returns, United remain short-handed. Matheus Cunha is ruled out for Palace but is expected back for the midweek clash against West Ham.
Benjamin Šeško and Harry Maguire remain unavailable, with Amorim stressing both will "take a little bit longer."
Crystal Palace boss Oliver Glasner confirmed that captain Marc Guéhi will start on Sunday after being substituted at half-time in Thursday's defeat to Strasbourg.
Will Hughes is also likely to feature despite a minor knee issue, while Borna Sosa is out.
Man United sit 10th but remain only three points off the top four heading into the weekend.