The Royals, unbeaten at home in 2010, scored twice in the closing minutes of the first half and never looked back, adding three more after the break.
Reading signalled their intention right from the start and, in the second minute, a free-kick on the left from Gylfi Sigurdsson was headed just wide of the post by Grzegorz Rasiak.
Moments later Richard Hinds had to hurriedly balloon the ball over his own crossbar as Reading striker Simon Church raced in to challenge.
The Owls hit back with Adam Federici diving low at his near post to keep out Michael Gray's effort, but it was Reading who came close again after 21 minutes when Lee Grant make an instinctive one-handed save from a close-range Rasiak header.
Reading finally made the breakthrough three minutes before the interval when Jimmy Kebe unleashed a fierce drive which flicked off Hinds before flashing past Grant.
On the stroke of half-time Reading added a second. Sigurdsson's left-wing cross was helped on by Church, leaving Rasiak a simple task to tap home.
Eight minutes into the second half Reading went further ahead with a stunning goal from Church. The Wales international striker was put clear by Rasiak, beat the marking defender and, from the edge of the box, unleashed a fierce shot past Grant.
With 25 minutes left Rasiak added his second from close range, after good work by Kebe, who then scored the fifth himself 19 minutes from time to earn Reading their biggest win of the season.
Manager Brian McDermott had the luxury of being able to replace Kebe, Church and Sigurdsson with substitutes in order to rest them before next weekend's FA Cup tie against Aston Villa.
This was a third successive defeat for Sheffield Wednesday boss Alan Irvine, with his side failing to score in any of those games.