The reigning champion edged a match that never dipped below elite standards, prevailing in a sudden-death leg after Woodhouse had dragged himself back from 3-1 down to force a final-set shootout.
Humphries' perfect leg came early, achieved via the classic 180, 180, 141 combination, and set the tone for a contest that saw both players average well into three figures.
Humphries finished on a 105 average with ten 180s, while Woodhouse pushed him relentlessly with an average just under 103.
The nine-darter doubled Humphries' set advantage and sent Arena MK into uproar, yet it proved no knockout blow. By the time Humphries led 3-1, both men were averaging north of 105, an extraordinary standard sustained across six sets.
Woodhouse refused to yield, levelling at 3-3 before Humphries missed three match darts and was forced into a winner-takes-all leg. The defending champion eventually closed out the match by pinning 54 with his final dart, a nerveless end to one of the tournament's defining ties.
"When I hit those two 180s, I just felt like it was going to go," Humphries told reporters afterwards.
"It was a great moment, but if I don't win the match, it means nothing, so I'm really glad I got the win to go with it."
Littler rolls on
Elsewhere on a packed third day of action, Luke Littler underlined his credentials as a leading contender with a commanding 4-1 victory over Ross Smith.
Littler opened the match with legs of 11, 13, 12 and 13 darts, storming into a 2-0 lead and briefly threatening the tournament record average as he averaged over 116 across the first three sets.
Although Smith, a former European Champion, recovered to take a set while averaging above 102, Littler closed the contest with clinical 120 and 92 finishes to seal a 107.88 match average.
"I played very well tonight, far better than Friday," Littler said. "That's what I had to do against Ross.
"We always have brilliant games, so I'm just glad to get through."
The Nuke's reward is a quarter-final against Josh Rock after the Northern Irishman produced a similarly authoritative display to beat Rob Cross 4-1.
Rock's performance was built on relentless scoring efficiency, with only seven trebleless visits across the entire match. He reeled off five consecutive legs late on to dispatch the former world champion, finishing with an average above 101.
"It would be fantastic to have a run here - it's my first time in the quarter-finals, and I'm looking forward to the game tomorrow," Rock said, setting up what is widely viewed as the standout tie of the last eight.
Danny Noppert delivered the most one-sided result of the round, whitewashing Stephen Bunting while conceding just a single leg. The Dutchman's sharpness on the doubles, converting 50 per cent of his attempts, contrasted sharply with Bunting's struggles on the outer ring and earned Noppert a quarter-final meeting with Humphries.
Price knocks out pal Clayton
In the early session, Gerwyn Price also progressed after a tense 4-3 victory over Jonny Clayton in an all-Welsh battle.
Trailing 2-0, Price turned the match with four ton-plus checkouts and, despite missing five match darts in the final set, held his nerve to win the deciding leg in 14 darts with a 102 average overall.
Gian van Veen continued his impressive rise with a 4-2 win over Nathan Aspinall, capitalising on a decisive edge on the doubles.
Van Veen converted 56 per cent of his chances compared to Aspinall's 19 per cent, rallying after an early onslaught in which Aspinall averaged over 110 in the opening exchanges.
The Dutchman now faces James Wade, who came from 2-0 down to defeat Gary Anderson 4-3, highlighted by a trademark 120 finish and a costly bust from Anderson in the final set.
Chris Dobey completed the quarter-final line-up with a gritty 4-3 victory over Damon Heta. Dobey nearly surrendered a 3-1 lead as Heta surged back, but a crucial 127 checkout on the bull proved pivotal before the Bedlington thrower closed out the match to book a clash with Price.
Finals day takes place on Sunday at Arena MK, with the quarter-finals concluding the afternoon session before the semi-finals and final are played in the evening.
The format lengthens to best of nine sets in the last four and best of 11 in the final, with £100,000 awaiting the champion.