Clayton had earlier beaten defending champion Luke Humphries 6-5 in the quarter-finals with a bullseye checkout after his opponent had missed double 16 to win it just seconds before.
The Welshman then beat Josh Rock in the semi-finals to reclaim top spot in the Premier League standings after Luke Littler had earlier limped out at the quarter-final stage with a defeat by Stephen Bunting that saw the sub-par world champion register an average of just 83.94 - his lowest ever average in a televised PDC match.
Van Gerwen, meanwhile, had impressed to beat compatriot Gian van Veen in the quarter-finals, but showed none of that form as he battled past Stephen Bunting 6-5 in an out-of-sorts semi-final performance.
The Dutchman had looked on course to rectify that when he broke Clayton twice in the final to take a seemingly insurmountable 5-2 lead with a chance to throw for the match. But then came the Clayton fightback, with MVG missing two match darts at double 16 to allow Clayton to break back, before going on to win on his own throw to move within one leg of the seven-time champion.
Clayton then provided another sensational bullseye finish to break Van Gerwen in the tenth, then rattled off a pair of 180s in the final leg to register his third win of the Premier League season following victories in Glasgow and Nottingham.
"I thought the game was over. He missed and gave me a chance. We’ve got to take chances," Clayton told Sky Sports.
"The last leg was probably my best of the game but they all count, I’m through, back on top of the table and it’s time for Luke Littler to start chasing me again.
"I know what it’s like to be here, I’ve got the experience, I know what it takes to get to Finals night. You’ve got to play darts, taken your chances, and if you play half-decent you’ve got a chance of playing on Night 17.
"I lost to Josh Rock last week, and the week before. Last week’s game was brilliant – Josh hit every double going. That puts you under pressure. I was just looking for two points coming into tonight, anything else was a bonus. So to end the night back in top spot, with another trophy for the cabinet is great."
The grit shown by the 51-year-old Welshman was all the more impressive given he had come into Night 10 having failed to win any Premier League match since beating Humphries in the final in Nottingham in Week 6.
Humphries himself has struggled to find his best in this campaign despite sweeping all before him last year. He now finds himself seventh in the standings after ten of the 17 events that determine which four progress to Finals night.
His quarter-final exit will be a disappointment, but the really disappointing quarter-final losses were those of Littler and Van Veen, who were on a collision course for a semi-finals showdown a week on from a heated clash between the pair in Week 9 that has many predicting an entertaining rivalry between them in the years to come.
But both were unable to progress to that semif-final as the wait for a first meeting since their frosty exhange in Manchester goes on.