Following up their 1-0 triumph at Old Trafford earlier in the campaign, the Eagles were in the ascendancy right from the get-go and were two goals up at the break courtesy of Michael Olise and Jean-Philippe Mateta.
Normal service resumed in the second period, where Olise notched his second of the night after Tyrick Mitchell had also got in on the act, moving the 14th-placed hosts onto 43 points as they end a troubled campaign with a flourish.
Oliver Glasner's men may still be seven places below Erik ten Hag's troops, but they outclassed their meek opponents in every department to leave the Red Devils below Chelsea in the final European spot on goal difference, and it is now 81 goals shipped for the permeable visitors, surpassing the 80 they let in during the 1977-78 term.
Once again sporting an incredibly youthful bench and makeshift defence, Man United were also ruing the rare absence of captain Bruno Fernandes, whose omission saw Mason Mount make a rare Premier League start.
Mateta matches Shearer feet against appalling Red Devils
The ageing backline of Jonny Evans and Casemiro immediately came under siege by the Olise and Eberechi Eze-inspired hosts, and Ten Hag's centre-backs were among the Red Devils men who failed to cover themselves in glory for a somewhat comical Palace opener in the 12th minute.
Latching onto a throw-in between the lines with no real pressure, Olise shrugged off Christian Eriksen and beat an onrushing Casemiro all ends up before charging at Evans, who just backed off and backed off against the advancing Frenchman.
With not a single Man United player prepared to put a tackle in, the Frenchman had ample time and space to pick out the bottom corner from the edge of the box, thereby registering his eighth strike of the Premier League season.
The Red Devils' response was feeble for the most part, but the ball was in the back of the Palace net in the 27th minute, when Dean Henderson would seemingly catch Casemiro's looping header, but the Eagles shot-stopper was nudged in the back by Rasmus Hojlund and the goal was chalked off.
There were shades of the David Raya vs. Bournemouth incident as Man United were controversially denied a leveller, and the visitors quickly returned to their meek ways, allowing Palace to punish them again in the 40th minute.
A calamity of errors on the right saw Palace regain possession through Chris Richards, whose through ball to Mateta ended with the Frenchman gliding past Evans as if he was not there and firing a fierce drive past Andre Onana.
Casemiro horror show continues in second half
Mateta emulated Alan Shearer with his strike, becoming the first man since the ex-Newcastle United forward in 1996-97 to score in each of his first six Premier League home games under a new manager, whose opposite number Ten Hag held off on making any half-time changes.
It was deja vu for Man United in the second period, as Casemiro had another goal ruled out for offside in the 53rd minute, and the Red Devils subsequently came under the cosh once more.
Onana managed to forestall Mitchell and Will Hughes within the space of a few seconds, but the Cameroonian was powerless to deny the former his hard-earned goal in the 58th minute, as he tapped in from unmissable range after Joachim Andersen prodded Wharton's delivery into his path.
The visitors' embarrassment went up a notch in the 68th minute, when the lackadaisical Casemiro was robbed of the ball on the byline by Daniel Munoz, who sprayed the ball to Olise just inside the box, and the winger's venomous drive flew past Onana's futile reach.
One could even argue that the 4-0 scoreline flattered Man United, who were all over the shop defensively and were fresh out of ideas in the final third too, not that they enjoyed many forays into the Palace half anyway.
Substitute Odsonne Edouard nearly made it a five-star performance from the hosts in added time, clipping the post with an effort that left Onana stranded to the spot, but Glasner's men ultimately declared at four.
The Eagles' final road fixture of the campaign takes them to Wolverhampton Wanderers on Saturday, while Man United return to face the discontent Old Trafford faithful on Sunday, hosting none other than leaders Arsenal.