Reigning World Matchplay champion van Gerwen continued his charge towards a second successive Blackpool triumph with a dominant display against Chisnall as the pair met at this stage for the third time in four years.
The world number one punished a slow start from Chisnall to open up leads of 2-0, 5-1 and 10-2 before the number nine seed sparked his challenge into life with a 116 checkout in leg 13.
Van Gerwen replied with a 106 finish, but Chisnall cut the gap to 12-7 and 13-8 before a 130 checkout from the Dutchman moved him two legs away from victory.
Chisnall replied with a 106 finish, but van Gerwen was too strong and finished 72 and 76 in the next two legs to secure his spot in the last four.
"I wasn't at my best tonight but I did enough to win the game," said van Gerwen. "Dave didn't turn up early on but I did the right things and the right time to win the game.
"I didn't play fantastic darts and I made a couple of mistakes but I won the game and that's the important thing.
"I feel comfortable but I'll have to concentrate in the semi-finals and be focused and punish Adrian when he makes mistakes because he always tests me. I'm looking forward to it."
Lewis edged past Peter Wright with a hard-fought 16-14 victory in a tight contest, which saw the Scot land a ten-dart finish and 12 maximums only to be knocked out as the 2013 finalist produced a superb second half to the contest.
A nervy opening saw Lewis lead by two legs on three occasions as he moved 2-0, 4-2 and 6-4 up only to be pegged back on each occasion by Wright, who then moved 8-7 and 10-8 up.
Lewis, though, produced a stunning five-leg burst to turn the game around, hitting two 14-darters, and 11-darter and a 12-dart finish as he moved into a 13-10 advantage.
Wright pulled back to 15-14 as Lewis twice failed to close out victory, but the Stoke star landed his ninth 180 before finishing double 13 for a 12-darter to finally seal the win.
"It was a battle," admitted Lewis. "We started slowly but it ended up being an awesome game and in the last ten to 15 legs I thought I played really well and I had to do that.
"The first half of the match we weren't scoring or finishing well, but the second half was fantastic and it was like someone flicked a switch on both of us. The last leg was great and it was a massive double 12 for me.
"Winning this tournament is my main target and I want to perform all the way through the match in the semis because I'll have to do. I can relax and enjoy the semi-final and I'm looking forward to it."
The quarter-finals conclude on Friday with the remaining two games, as 15-time World Matchplay champion Phil Taylor plays Mervyn King before World Champion Gary Anderson takes on Steve Beaton.
Following his quarter-final victory, van Gerwen has been cut from 4/5 to 4/7 as the odds-on favourite with sponsors BetVictor to claim the £100,000 title on Sunday evening.
Lewis has moved in from 14/1 to 8/1 following his quarter-final win, with Anderson the 3/1 second favourite, Taylor 5/1 and outsiders Beaton and King both 66/1.
BetVictor World Matchplay
Thursday July 21
Peter Wright 14-16 Adrian Lewis
Michael van Gerwen 16-9 Dave Chisnall
Friday July 22 (7pm-11pm)
Mervyn King v Phil Taylor
Gary Anderson v Steve Beaton
Quarter-Finals - Best of 31 legs
Peter Wright v Adrian Lewis
0-1 - Lewis lands a 180 before finishing double 18 to win the opener.
0-2 - The Stoke ace takes out 92 to break throw.
1-2 - Lewis misses tops for a 125 finish, and Wright takes out 80 with two double tops to claim his first leg.
2-2 - Wright initially misses six darts at doubles, but Lewis is unable to land double 12 and six with three darts as the Scot returns to finally hit double five as he levels.
2-3 - The double trouble continues as both players miss their chance to regain the lead before Lewis returns on double four.
2-4 - Lewis fires in a 180 before hitting a third-dart tops to break throw and move two legs clear.
3-4 - Wright hits his first 180, and is able to return from a missed bullseye to land double eight, after Lewis misses two darts to extend his lead.
4-4 - Wright levels once again, taking out 64 on double 16.
4-5 - Lewis opens with a 180 before punishing Wright's miss at tops, for a 116 finish, by hitting the same bed.
4-6 - Lewis fires in a 180 to leave 20, but Lewis takes out 97 on double 12 for a pressure shot to regain his two-leg lead.
5-6 - Wright hits his third 180 and double ten as he responds.
6-6 - Wright once again levels.
6-7 - Lewis takes out 20 to move back in front.
7-7 - Wright hits a 180 and double 12 to square the game.
8-7 - A fifth 180 for Wright is followed by double eight - after Lewis misses the bull - as he moves ahead for the first time.
8-8 - Lewis produces his best leg of the match, landing two maximums in an 11-darter to hit back.
9-8 - Wright fires in a 180 and double 18 as he regains the edge.
10-8 - Wright moves two legs clear for the first time, hitting another maximum and tops.
10-9 - Wright lands his eighth 180, but Lewis hits double six to cut the gap.
10-10 - Wright misses the bull for a 161 finish and a further three darts to win the leg, allowing Lewis back from one miss to land double two to level.
10-11 - Wright opens with a maximum, but Lewis responds with a 180 of his own before finishing 82 on double 16 for another 11-darter.
10-12 - Lewis hits double six to complete a 12-darter as he regains a two-leg lead.
10-13 - Lewis takes a fifth successive leg despite a tenth 180 from Wright, finishing 72 on double 12.
11-13 - Wright fires in another maximum before hitting double 12 to complete a 13-dart finish to claim his first leg in six.
11-14 - Lewis finishes 44 on double 16 to regain his three-leg lead.
12-14 - Lewis opens with a 180, but sees Wright also land a maximum before taking out 68 to hit back.
12-15 - Double nine sees Lewis move a leg away from victory and a semi-final place.
13-15 - Lewis lands a 180 but wires double ten for a 140 finish, and Wright keeps the match alive on double 16.
14-15 - Lewis initially misses three more match darts before then bursting his score, and Wright steps in again on double 16 to to save the game and cut the gap to one leg.
14-16 - Lewis opens with his ninth 180 and is first to a double before finally sealing the win by taking out 81 on double 13.
Michael van Gerwen v Dave Chisnall
1-0 - van Gerwen opens the game with a 180 and punishes Chisnall for one miss by landing double five to break throw.
2-0 - Double four sees the reigning champion move two legs up.
2-1 - Double 16 gives Chisnall his first leg of the game.
3-1 - Both players land 180s before van Gerwen finishes 94 with a single 18, double 18, double top combination.
4-1 - Chisnall misses two darts at tops, and van Gerwen hits the same bed to open up a three-leg lead.
5-1 - Double top sees van Gerwen move four legs clear.
5-2 - Chisnall responds with double top.
6-2 - Both players land 180s before van Gerwen posts double 16 to move clear again.
7-2 - van Gerwen teases a nine-darter with two 180s, and though he is unable to complete a perfect leg he returns to finish double 16 for a 13-darter.
8-2 - van Gerwen lands another maximum, his fourth in three legs, as he opens up a six-leg cushion.
9-2 - Double eight sees van Gerwen continue his charge.
10-2 - The Dutchman finishes 48 on tops to move eight legs clear.
10-3 - Chisnall takes out 116 to respond.
11-3 - van Gerwen posts a 180 and a 106 finish to regain his advantage.
11-4 - Chisnall lands a 180 before punishing van Gerwen's missed bullseye, for a 122 finish, with double two.
12-4 - van Gerwen hits a maximum and double ten to move four legs away from the semi-finals.
12-5 - Double eight sees Chisnall respond.
12-6 - Chisnall lands a 180 before hitting double seven to break throw for the first time in the game.
12-7 - van Gerwen lands a 180 but sees a miss at double five allow Chisnall in on double ten.
13-7 - Double ten sees van Gerwen win his first leg in four.
13-8 - Chisnall takes out 52 to continue his revival.
14-8 - Chisnall opens with a 180 but sees van Gerwen take out 130 on double five.
14-9 - van Gerwen fires in a 171 score, but Chisnall takes out 106 for his second ton-plus finish.
15-9 - van Gerwen finishes 72 on tops to move a leg away from the win.
16-9 - Chisnall misses a dart at tops, and van Gerwen finishes 76 on double eight to complete the win.