The Morecambe ace was beaten 16-9 at the Winter Gardens as the world number one marched towards a successful title defence.
The Dutchman retained his title with a 17-9 victory over Adrian Lewis in the semi-finals before getting the better of Phil Taylor, 18-10, in Sunday’s final.
The triumph saw van Gerwen become only the third player - alongside Taylor and Rod Harrington - to retain the prestigious World Matchplay title, as he retained the trophy and pocketed a £100,000 first prize as he won a 12th tournament of 2016.
The champion had punished a slow start by Chisnall, who swept aside Benito van de Pas and Robert Thornton in the first two rounds, in the opening stages of their quarter-final on Thursday.
Van Gerwen opened up leads of 2-0, 5-1 and 10-2 before the number nine seed sparked his challenge into life with a 116 checkout in leg 13.
The Dutchman replied with a 106 finish, but Chisnall cut the gap to 12-7 and 13-8 before a 130 checkout from the Dutchman moved him two legs away from victory.
Chisnall replied with a 106 finish, but van Gerwen was too strong and finished 72 and 76 in the next two legs to secure his spot in the last four.
On winning the title, van Gerwen said: “It feels amazing to win this title again.
“I think I won this title quite comfortably but I did the right thing at the right moments in this tournament and I didn’t make a lot of mistakes.
“I think I’m the best but you need to show it on that stage, especially in moments like that.”
The PDC schedule moves onto the next European Tour event in Dusseldorf this weekend.