Wakefield were missing Steve Nicholson through injury so Ryan Bent started at right back. The only other change from Saturday's draw at Chorley was at left back where Phil Turner returned after a long injury lay off in place of Jack Koleszar.
The visitors went in front on 7 minutes when Wakefield goalkeeper Jan Zolna fouled in the area and captain Michael White stepped up to convert the penalty.
Zolna then had to be alert to get down well and make a good save from Skelmersdale's Steve Burke shortly afterwards.
Wakefield equalised on the quarter hour marker when Marc Roberts stooped to place a header past Ryan McMahon at the far post.
Both sides were struggling to create chances in a fiery encounter and it wasn't until the last fifteen minutes that the game came to life.
Wakefield right back Ryan Bent was dismissed for a second booking after a foul out on the wing and minutes later Mark Houghton put Skelmersdale in front with a powerful shot that screamed past Zolna into the goal.
The home side tried to come back at Skelmersdale but the closest they came to a goal was a Phil Turner free kick that flew inches over the bar.
Wakefield then had another player dismissed at the death as centre half Craig Laight was shown a second yellow card for a bad challenge on the edge of the 18 yard box.
Wakefield FC Man of the Match: Marc Roberts.
Wakefield: Zolna, Bent, Turner, Roberts, Milnes (c), Laight, Shooter, MacManus, Thompson (Noteman 75), Jones, Ferguson (South 85). Subs Not Used: Pleasants, Koleszar, Danville.
Attempts at Goal: Wakefield 3 Skelmersdale United 10
On Target: Wakefield 1 Skelmersdale United 5
Corners: Wakefield 2 Skelmersdale United 7
Offsides: Wakefield 4 Skelmersdale United 2
Fouls: Wakefield 13 Skelmersdale United 6
Yellow Cards: Wakefield 4 (Laight 37, 90+2, Bent 45, 74) Skelmesdale United 1 (S Burke 37)
Red Cards: Wakefield 2 (Laight Bent 74, Laight 90+2)