Welshman Clayton served a minor upset by beating Stephen Bunting 16-7 in Blackpool.
The Welshman set the tone with an 11-dart leg to open, then landed a sublime 160 checkout to race into a 5-0 lead, averaging 110 in the process.
Bunting managed to steady himself and share the next ten legs, but Clayton never looked threatened.
He added another 11-darter en route to an 11-6 lead, and when Bunting briefly narrowed the gap with a 12-darter of his own, Clayton responded with four straight legs, highlighted by clinical checkouts of 76 (twice), 108 and 118, to end proceedings in style.
“I love this tournament,” declared Clayton, the runner-up at the Masters and a UK Open semi-finalist in 2025.
“Total respect to Stephen. I don’t think he played his best game tonight, but I played well and put him under pressure.
“I’m playing against one of the best players the world of darts has ever seen in James Wade.
“If I want to win this tournament, I have to beat him. I’ve got a big heart and I’m a proud man, so hopefully I’m here until the end.”
Earlier, Wade got the better of the Netherlands' Gian van Veen (16-13) in the first quarter-final.
Now 42, Wade is the last former champion (2007) left standing and continued his enduring love affair with the Matchplay, reaching a remarkable tenth semi-final.
It was far from vintage Wade early on. He missed his first 11 darts at double, gifting Van Veen a 4-1 lead. But the Englishman reeled off eight consecutive legs with clinical finishing, landing combination checkouts of 68, 86, 80 and 61, to seize control at 9-4.
Van Veen responded with a spirited rally and clawed back to 13-11, but two missed darts at double 16 in a crucial 25th leg proved costly. Wade punished the error and held firm in the closing stages to edge over the line.
“I’m so, so happy. I’m buzzing,” reflected Wade, also a five-time runner-up at this event.
“I think in my first two games I was one of the best players in this tournament, but that was a scrap up there tonight.
“I was so disappointed with the way I started, but I did what I needed to do, and I was fortunate that Gian didn’t make the most of his opportunities.
“I thought I had thrown it away because he was coming back towards the end of that game, so I’m very grateful to go through.”
The two remaining quarters will be contested tomorrow night, as Luke Littler faces Andrew Gilding and Gerwyn Price takes on Josh Rock.