Despite the defeat, joint manager Jon Underwood later stated that he felt it was one of Slough's best performances of the season, and that his side had played better than when they beat Histon 7-1 in August.
Early on, Lewis Putman's inviting cross almost found Scott Harris, but he was unlucky to see a foul awarded against him.
Leamington responded with Connor Gudger flashing a cross across the face of goal, but Ben Mackey could not make contact. Soon after, Richard Taundry's free kick from out wide was fisted clear by Mark Scott.
Leamington took the lead with ten minutes played. Jack Edwards was unmarked in the box and headed past Scott and into the corner, though there were strong suspicions of offside in the build-up. Lee Chilton looked to have been in an offside position and interfering with play, but he made full use of the apparent confusion in the Slough defence to cross for Edwards to score.
Slough almost responded with a scuffed effort from Scott Harris after he was played in by Adam Martin, but the ball bounced back off the post with the deceived keeper Tony Breeden well beaten.
On 25 minutes, the hosts doubled their lead with a well-worked goal. Ben Mackey was able to take a touch on the edge of the box and fire a left-footed effort inside Scott's near post. The goal came from Chilton's inch-perfect diagonal ball from the left over the head of Jhai Dhillon, which Lee Moore on the right wing controlled. He then teed up Mackey to beat the dive of Scott.
Eleven minutes later, Leamington scored a third, with Edwards heading in his second goal at the back post following a short corner. Ben George picked up the ball and had plenty of time to chip in for Edwards to beat Scott again.
Slough had not played badly, but found themselves three goals behind due to moments of slack defending and clinical finishing.
The Rebels went on to enjoy large spells of pressure in the second half. Early on, Ryan Hope - making his first start for the Rebels - forced Breeden into a save, and Scott Harris dragged a shot wide of goal.
Dan Hicks, making his first start back at the club, saw a shot blocked after a storming run through midfield, and then Leamington broke down the right hand side and forced Scott into a good one-handed save.
Putman, again looking a threat, hit a long-range strike which Breeden palmed away, with Warren Harris shooting wide from the rebound.
On the break, Leamington always looked as if they could find a fourth goal; Gudger almost produced it with a neat turn and shot, but the ball flew inches wide of the upright.
Taundry fired a 25 yard free kick into the side netting, but Slough did not give up and Hope also tried his luck from distance, but the ball was deflected behind for a corner.
Chilton could have rounded the scoring off in spectacular fashion when he picked up a pass from Gudger on halfway and embarked on a long, mazy run, but he put his shot just over Scott's bar from the edge of the box.
Slough now turn their attention to the visit of Bideford on Saturday.
Leamington Line up
Tony Breeden (c), Ben George, Connor Gudger, Joe Magunda, Jamie Hood, James Mace, Lee Moore, Richard Taundry, Ben Mackey, Jack Edwards, Lee Chilton. Subs: Will Green, Ross Oulton, James Fry, Rob Ogleby, Edward Caviezel-Cox.