The Eagles have crossed swords with the Red Devils on a regular basis since the English top-flight underwent a makeover in 1992.
Palace have spent time out of the top tier, but had faced United on 20 occasions heading into a latest showdown on Saturday.
No victories had been collected from those previous outings, with just four points collected down the years.
Only one of those had come at Old Trafford, with a 0-0 draw played out last season.
Palace finally boast bragging rights over the Red Devils following a dramatic encounter at the Theatre of Dreams.
Jordan Ayew fired them in front in the 32nd minute, with United well short of their best in the first half.
Ole Gunnar Solskjaer’s side then spurned a glorious opportunity to level matters as Marcus Rashford missed from the spot.
Daniel James appeared to have rescued a point when he netted a minute from the end of normal time, but there was to be one more twist in the tale.
An uncharacteristic error from David de Gea allowed Patrick van Aanholt to drive home a stoppage-time winner.
90 - Patrick van Aanholt has become only the second ever player to score a 90th minute winner vs Man Utd in the Premier League, after Thierry Henry with Arsenal in January 2007. Van Aanholt is the first to do so in a match at Old Trafford. Incredible. #MUNCRY pic.twitter.com/uITm70IWZV— OptaJoe (@OptaJoe) August 24, 2019
He is only the second man to have netted beyond the 90th minute to claim a Premier League win over United, and the first to do so at Old Trafford.
Thierry Henry is the only other player to have downed the Red Devils in that style.
Palace now have plenty to celebrate after finally get one over on United.
Having become accustomed to slipping up in Premier League action, a long wait for a win has come to an end.
Their last triumph over United came way back on May 11, 1991.
They prevailed 3-0 that day, while you have to turn the clock back 30 years to find the Eagles’ last win at Old Trafford.
That came on December 9, 1989, with that contest also ending 2-1 in their favour.