Chesterfield took the lead inside the first minute after their winger used her pace and then slotted the ball into the bottom corner.
Wednesday came close to equalising two minutes later after a pass from Laura Gallego found Diana Garin, who saw her shot just go wide of the post.
Wednesday managed to equalise in the 17th minute after a brilliant pass from the back was played through to Monica Charles, who ran through and smashed the ball low and hard past the keeper.
The chances kept going Wednesday's way as Ellie King came close as a loose pass found her, but her shot went wide of the goal.
Chesterfield took the lead for the second time in the game when a ball was played over the top to a Chesterfield offside player who ran towards the ball. She left it to a player who was onside, and she passed it back for the offside player to tap it in. This, however, left all the Wednesday confused due to offside player interference with the first pass.
Abbie Timson was then forced into making a good save as she ran out of her goal to stop a one-on-one chance with the Chesterfield attacker.
Chesterfield went into halftime 2-1, but Wednesday's first-half momentum seemed to be put down by a harsh refereeing decision for Chesterfield's second goal.
The second half began, and not long in, Wednesday was awarded a penalty after Michaela Barrett was taken out by the Chesterfield keeper.
Chloe Rose took the penalty but saw her effort hit the crossbar and rebound back to her, causing an indirect free kick.
Chesterfield made it 3-1 as a pass across the box was tapped in at the back post to give them a strong grip on the game.
The game seemed to be finished after another goal was scored by Chesterfield after a pass was played in behind the Wednesday defence and the shot was stroked into the far corner to make the game 4-1.
The game ended in a 4-1 defeat for Wednesday Ladies Reserves.
The POTM was given to Laura Gallego for excellent performance once again in the middle of the pitch.
Wednesdays Ladies Reserves next game will be against Socrates on the 6th of April.