Wade edged the Australian ace 18-16 in a tie-break after a sensational display of darts from both players on Thursday evening.
The pair both averaged just shy of 100 in a marvellous match, which saw the lead change hands seven times.
“I am very happy to win because that was so hard,” said Wade, the world number four.
“Simon played very well and I had to respond to everything he threw at me. I still think I’ve got a little bit extra to give this week and I will need it against Phil.
“I feel very comfortable here and I have again shown I have what it takes in a big match. I’m looking forward to the semi-finals now and I will get my preparation right.”
The first two legs both went against the throw before Wade produced a fine 120 finish to hold.
Whitlock checked out 50 but Wade edged back ahead by pegging double ten, after missing double top to go out on 150.
‘The Wizard’ cleaned up 66 to level again before two 180’s helped Wade take a 4-3 lead.
But Whitlock took the next three legs, including a 92 finish on the bull to move 6-4 infront.
‘The Machine’ then put together a fantastic run of four legs in a row, hitting double top to win each of them, as he went 8-6 up.
Whitlock hit back by taking out 60 and then a wonderful finish of 130 on the bull to restore parity, before the Australian moved ahead with a 92 finish to break his opponent’s throw.
The 2007 champion responded by taking out 51 to break and he moved within a leg of Whitlock by holding.
The former European Champion restored his two leg lead but Wade stayed in touch with a 56 finish after hitting a 174.
Both players started the 28th leg with maximums and Wade levelled up at 14 all with a stunning checkout of 135 on the bull.
‘The Machine’ then held his throw to edge ahead and Whitlock did the same to force a tie break situation.
Three legs went with the throw before ‘The Wizard’ was punished for two missed darts at doubles, as Wade cleaned up 58 to win an absolutley thrilling match.
The world number four will take on Taylor in the semi-finals on Saturday.
By Chris Murphy
See James Wade compete with Steve Brown at the Anglo-Dutch Masters versus Michael van Gerwen and Raymond van Barneveld in December – Tickets on sale now.