A long-range effort from Sampson less than 20 seconds in was added to by a Jack King penalty just three minutes later, with Matthew Platt pulling a goal back on seven minutes.
Didcot restored their two-goal cushion as Williams bundled in from a corner, but Slough responded well in the second half with a goal from James Pritchard. However the Rebels were thwarted in their attempts to score an equaliser as Dean Harper saw red for a second bookable offence.
It was a terrible start from the Rebels, who weren’t switched on from the start and allowed 17 year old Sampson, on loan from Oxford United, to find space and unleash a shot from 30 yards which arced over Jamie Jackson’s head and into the top corner.
Slough could have gone two down just a minute later as King blazed over from the edge of the box, but the midfielder made no mistake from the spot after Ricky Allaway was penalised for handling a cross in the box. King coolly placed his kick into the bottom corner to give Slough a mountain to climb so early on.
Just three minutes later, Platt restored hope for the Rebels, finishing expertly with the outside of his right boot from out wide after Watkins had made a mess of an attempted clearance with Yashwa Romeo bearing down on him.
Romeo missed a chance to level the scores soon after, wriggling free from his marker but hitting a weak shot straight at Watkins.
Predictably, the game settled down after the frantic start but Didcot looked the more threatening and made it 3-1 on 24 minutes as defender Williams scored from a corner, the ball appearing to hit him and squeeze through Jackson's legs.
Slough needed to find a quick response, and Pritchard squandered a good chance when he volleyed a knockdown from Allaway straight at Watkins.
Slough emerged in the second half full of purpose and Matthew Platt was in the thick of the action, having a rising drive tipped over the bar followed by a near-post attempt after Romeo had had his shot blocked.
Dean Harper's header from Pritchard's free kick cannoned back off the crossbar and left Rebels fans wondering if this was going to be another frustrating afternoon.
Didcot had a great chance to wrap up the victory when Sampson broke and escaped the attention of Fenton and got free down the right, but Jamie Jackson spread himself well to save.
Slough got the glimmer of hope they were looking for on 69 minutes as smart interplay led to Makh playing in James Pritchard, who took his time before placing the ball into the bottom corner past Watkins.
That hope diminished somewhat minutes later as Dean Harper's late challenge led to a second booking and a sending off, his second of the season.
Despite this, Slough threw caution to the wind and continued doing most of the attacking, but looked to have lost the impetus and were unable to force any further chances. Former Rebel Michael Bartley had the best chance in the dying stages for Didcot, but his effort from out wide was cleared off the line after Jackson had gone out to challenge the striker.
Didcot held on for what was, on balance, a deserved three points, and Slough now look ahead to the away game at Thatcham to try and kick-start another unbeaten run.
Didcot Town Line up
Watkins, Heapy, Jack, Williams, Brown, Howell (Mortimer-Jones), Sampson, King, Bartley, Roach (Hodgkins), Powell. Subs not used: Saunders, Buckner.