First half goals from Jordan Smylie and Jamie Craig sealed the win for the Northern Suburbs outfit whilst Jordan Hall scored the only goal for the Wanderers, who now fall to fifth place in the NPL 2 after their defeat.
With first choice left-back Mathieu Cordier ruled out on the morning of the game and another four starters selected in the squad for Saturday's blockbuster clash against Arsenal, a number of players from the U18 and U20 Academy squads were called up into the NPL 2.
The Wanderers were forced into some defensive work early on with Abdelrahman Kuku blocking a shot from Tigers forward Smylie.
Midway through the first half, the Tigers took the lead, Smylie finishing past Syron after getting on the end of a long ball.
Then, with just under 10 minutes left in the first half, Northern Tigers doubled their lead, as a cross from Jamie Craig was deflected into the Wanderers goal.
After the interval, the Tigers pushed hard to kill the game off but the Wanderers defence stood firm.
Five minutes into the restart Syron pulled off an amazing save tipping a close range shot onto the crossbar.
Lachlan Campbell was also up to the task intercepting a number of through balls and making some crucial headed clearances.
With 20 minutes left in the match, the Wanderers pulled one back.
Oliver Pufflett did well to reach a loose ball and play it into the six-yard box with Jordan Hall providing the finishing touch and scoring his first goal for the club.
The Wanderers went close to equalising after substitute Tacettin Kumsuz found Puflett with a fantastic through ball only for his shot to fly over the crossbar.
In the final minute, the Tigers almost got their third goal, but once again Campbell came to the rescue deflecting a shot onto the crossbar.
The loss, combined with a win in the U18s and a loss in the U20s, sees the Wanderers stay in 3rd place in the NPL 2 Club Championship.
The Wanderers will next play St George FC at Sydney United Sports Centre.
Northern Tigers 2 (Jordan Smylie 22’ Jamie Craig 36’)
Western Sydney Wanderers 1 (Jordan Hall 70’)
Western Sydney Wanderers: Mackenzie Syron, Malcolm Ward (Tacettin Kumsuz 63’), Abdelrahman Kuku, Lachlan Campbell, Richard Stewart, Jordan Hall, Joshua Bartolotto, Charles Abou Serhal, Oliver Puflett, Brandon Stojcevski, Emmanuel Gonzalez (Anthony Vastag 63’)
Unused subs: Daniel Axford, Noah Pagden, Brandon Robertson
U20s: Northern Tigers 2-1 WSW
U18s: Northern Tigers 3-5 WSW
U15s: Blacktown City 2-1 WSW
U14s: Blacktown City 2-0 WSW