At 8-8, Wade missed double top to hand his fellow Englishman a chance to break his throw, but Humphries failed to hit the bull.
Wade sealed it with double 10 before Humphries squared the match with a 12-dart leg, despite Wade nailing back-to-back 180s.
In the deciding leg, Wade – who won the tournament in 2008, 2011 and 2021 – kept his cool to throw two maximums en route to a superb 11-dart leg, wrapping it up with double top.
“I was probably a little weak at the beginning and was quite grateful at the end that Luke missed opportunities and opened the door for me,” Wade said.
“It’s about timing and the young darts players need to learn it’s not about the big averages but timing the right things at the right time.”
Wade’s reward is a semi-final against Northern Ireland’s Josh Rock, who saw off a brief fightback from Nathan Aspinall to clinch a 10-7 win over the Englishman in his quarter-final.
The UK Open winner will pick up £110,000 in prize money.
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