Van Gerwen, the defending champion, appeared poised to secure his eighth Players Championship Finals title after hitting his third nine-darter in the tournament's history. He surged ahead with a 9-5 lead at Butlin's Minehead Resort.
Cazoo Players Championship Finals 2023
However, Humphries incredibly reeled off six successive legs to secure a third televised title inside two months and scoop the £120, 000 top prize.
Humphries' triumph adds to his victories in the World Grand Prix and Grand Slam of Darts during a busy autumn, propelling the 28-year-old to a career-best third place on the PDC Order of Merit.
"To stand here with my third major title, I can't put it into words!" said Humphries. "I never dreamed of winning one, let alone three.
"I'd love to have beaten Phil Taylor in a final but I never got that opportunity so the next best thing for me is [to beat] the great of our generation, Michael van Gerwen.
"To beat him in a final is what I always dreamed of. I watched this man seven or eight years ago being at the absolute peak of his career, winning everything [and hitting] 110 averages for fun.
"To beat him in a final, I think this one probably does mean the most to me.
"It means I'm the best player in the world - he said I had to beat him in a final and I did! Michael was fantastic there, but he allowed me in."
Humphries opened the final with a superb 130 bull finish, with Van Gerwen taking out 126 in response before claiming the final's first break of throw in leg five with his incredible nine-darter; landing back-to-back 180s before finishing 141 on double 12.
The pair then traded 14-darters and Van Gerwen landed a 13-darter to lead 5-3, with Humphries replying on double ten before missing double 18 to level in leg ten, as the reigning champion pinned tops for a 74 combination.
Van Gerwen then secured a second break of throw by finishing 90 in two darts to punish a missed bull from Humphries for a 164 checkout, before a 13-darter gave the world number two daylight at 8-4.
Humphries responded with back-to-back maximums in a 12-darter to claim his fifth leg, only for Van Gerwen to fire in a ten-dart leg to restore his cushion.
Another 14-darter saw Humphries hit back before he broke for the first time on double ten, and double five saw the gap reduced to one leg at 9-8.
Humphries then followed a 180 with a stunning 142 checkout to level he final, and continued his momentum with a third-dart double ten to move 10-9 up.
The tension rose as Van Gerwen battled to force a deciding leg, but the Dutchman missed eight darts at doubles to keep his hopes alive before Humphries finally pinned double one to close out a memorable triumph.
Humphries had defeated James Wade in Sunday afternoon's quarter-finals and averaged over 106 in his semi-final romp against Ryan Joyce, but admitted that he had to dig deep in the title decider.
"When I was playing that game, I felt flat, " he added. "Against Ryan I was so tired and in that game there I felt I had nothing to give but I kept grinding."
Van Gerwen, who was appearing in his ninth final in 11 years of the event, paid tribute to Humphries after their dramatic contest.
"I had my chances, " admitted Van Gerwen. "I was 9-5 up and from that position, I'm not allowed to lose; simple as that.
"I made it incredibly difficult and when you do that against a player in his form, you only can blame yourself.
"I had opportunities there but he played well at the end, he never gave up and fair play to him."
Van Gerwen had produced a tournament record average of 118.52 in Saturday's second round, and began Sunday's final day of action in Minehead by coming from 9-6 down against Stephen Bunting with a stunning burst of 13, 12, 11 and 12-dart legs.
He then averaged over 101 in a dominant 11-6 semi-final win over Gabriel Clemens, and added: "My level is definitely close to my best, but still you have to do it at the right moments.
"Today, I thought I was doing that but fair play to Luke. He played well all tournament, he's got the confidence, he's got everything on his side at the moment."
Clemens followed up his run to the World Championship semi-finals 11 months ago by seeing off Luke Woodhouse 10-7 in the last eight to match that achievement.
Ryan Joyce joined the German ace after his 10-6 win over Damon Heta secured a first appearance in a televised semi-final during a resurgent spell for the Newcastle thrower.
Sunday's action in Minehead also featured the Winmau World Youth Championship final, as 16-year-old sensation Luke Littler defeated Gian van Veen 6-4 to claim that title and a £10, 000 top prize.
Click here for match stats & results.
2023 Cazoo Players Championship Finals
Sunday November 26
Afternoon Session
Quarter-Finals
Michael van Gerwen 10-9 Stephen Bunting
Gabriel Clemens 10-7 Luke Woodhouse
Luke Humphries 10-7 James Wade
Ryan Joyce 10-6 Damon Heta
Evening Session
Semi-Finals
Michael van Gerwen 11-6 Gabriel Clemens
Luke Humphries 11-3 Ryan Joyce
PDC Winmau World Youth Championship Final
Luke Littler 6-4 Gian van Veen
Final
Luke Humphries 11-9 Michael van Gerwen
Source PDC