Colin Cameron had given them the lead with his first goal since September before Seyi Olofinjana doubled their advantage in first-half stoppage time.
Dean Morgan gave Reading hope when he struck at the start of the second-half but the damage had already been done.
Clarke put the result beyond doubt with two goals in the final 12 minutes as Wolves recorded their third win in six games under the control of caretaker boss Stuart Gray.
For Reading it was just their third defeat in 13 games. The result could have been a lot different if they had made the most of some long spells of domination.
Wolves were indebted to goalkeeper Michael Oakes for ensuring they stayed on level terms before Cameron and Olofinjana struck.
Twice in the space of four minutes Oakes denied Steve Sidwell with smart saves. He tipped a 20-yard shot by Sidwell over the bar in the 12th minute before turning away a header from the former Arsenal midfielder.
Failing to turn that early domination into goals proved to be costly for Reading.
They were first undone after 32 minutes when Cameron raced on to a flick from Olofinjana and steered a curling shot from 14 yards beyond Marcus Hahnemann.
Having had a hand in creating the first goal, Olofinjana then got on to the score sheet himself when he finished off a smart three-man move.
A flick by Keith Andrews was pushed into the path of Olofinjana by Dean Sturridge and the Nigerian international completed the move by pushing his shot past the stranded Hahnemann.
Wolves should have been in cruise control after opening up a two-goal lead, but Reading began the second half just as they had started the first - only this time they made their good play pay-off.
Morgan handed them a lifeline with a 47th minute strike that left Wolves fuming. The home defence was convinced that Morgan was offside when he raced on to a pass from Ricky Newman, but the flag stayed down and Morgan powered forward before drilling his low drive past Oakes.
Just as he had done in the first-half, Oakes then had to come to Wolves' rescue again after 73 minutes with a brave save at the feet of Lloyd Owusu.
Reading's comeback hopes were then extinguished once and for all 13 minutes from time when Clarke capitalised on a mistake by central defender Ibrahima Sonko.
The Senegalese stopper tried to shepherd the ball out of play but Clarke nipped in to dispossess him before beating Hahnemann at the near post.
Clarke then gave the final scoreline a somewhat flattering look when he raced on to a stoppage-time flick on from Carl Cort and volleyed home from 12 yards.