Palace lost goalkeeper Dean Henderson, signed from United in August, after 19 minutes of his club debut when he appeared to strain his right leg after what had looked like a straightforward long kick.
He was replaced by Sam Johnstone, another graduate of the Manchester United academy, who was picking the ball out of the net two minutes later when Diogo Dalot cut back from the byline for Alejandro Garnacho to sweep in right-footed.
Anthony Martial scored the third in the 55th with his first goal of the season when he cashed in on some poor defending to run onto a Casemiro cross at the back post and fire past Johnstone.
The match was the night’s only fixture pitting two top flight clubs against each other and they will meet again in the league at Old Trafford on Saturday.
Wolves went 2-0 up and then lost 3-2 at Championship high-flyers Ipswich Town while Premier League newcomers Luton were beaten 1-0 at League One side Exeter City.
Exeter held on with 10 men after Demetri Mitchell was sent off for a second yellow five minutes after scoring his 83rd minute goal.
Vincent Kompany’s Burnley, without a win in the Premier League so far this season, overran League Two opponents Salford City 4-0 with a second-string team.