Wolves swept ahead in the 14th minute as Andy Keogh sped past full-back Tommy Spurr,cut in from the right flank and fired in a right-foot strike which was blocked by keeper Lee Grant's outstretched foot.
The ball spun to the feet of the lurking Eastwood who finished clinically with a low drive from ten yards.
The misery continued for the Sheffield side four minutes later when striker Francis Jeffers, a £700,000 capture from Blackburn in the summer, limped off after 18th minute to be replaced by Leon Clarke.
Wednesday carved out a chance in the 27th minute, winger Jermaine Johnson caused havoc on the right flank, before pumping the ball to the far post as Small headed over from the tightest of angles.
Wednesday were back on level terms in first-half injury-time, Glenn Whelan's corner was met by Johnson, his crisp strike was handled on the line by defender Michael Gray and Small hammered the loose ball into the net with Gray picking up a yellow card.
Wolves grabbed a second three minutes after the restart , Eastwood threading the ball beyond the reach of a string of defenders to Kightly who swept the ball past Grant from 12 yards.
Wednesday were prized open again minutes later, Kightly doing the damage with a strong run down the right, before crossing to Stephen Ward whose close-range shot was deflected.
Small was foiled by a last-ditch tackle by Kevin Foley and a Johnson cross hit the top of the bar and with minutes to go Wayne Hennessey clung onto his low drive as the ball almost crossed the line, before substitute Bothroyd added the third in injury time.