The game was effectively won in the opening 15 minutes as Matt Phillips continued his red-hot scoring streak with a precise finish and Lomana LuaLua curled in a superb effort soon after.
The Seasiders produced an outstanding attacking display and they made it three shortly after the break with another goal of sheer quality, Ludovic Sylvestre bending in from the edge of the area.
It could, and perhaps should, have been more but with the quality of all three goals, Blackpool manager Ian Holloway will have seen enough to be confident of going to Goodison Park and forcing a result in 11 days.
For Wednesday, it was a night to forget, although with an npower League One promotion assault to concentrate solely on now, boss Gary Megson may not be too disappointed.
The fact that Megson made eight changes from the Owls' weekend win over Yeovil highlights exactly where he ranked this game in importance, though Holloway, whose side sit fifth in the npower Championship, also made eight changes.
Despite that rotation, it was an open start and Wednesday had already spurned a golden chance as Ryan Lowe shot straight at Matt Gilks when offered a clear sight of goal by the time Blackpool went ahead in the seventh minute.
Some neat passing saw Phillips receive the ball 20 yards out and through a crowded area he skilfully picked his spot in the bottom corner with goalkeeper Stephen Bywater possibly unsighted.
It continued a remarkable run of form for the 20-year-old, who made it 10 goals in 10 games and three in the space of 14 minutes of action after his late double at Cardiff on Saturday.
He will have been especially pleased to bag on his return to Sheffield, where he scored six in seven appearances for Wednesday's city rivals United when on loan earlier this season.
Blackpool doubled their lead seven minutes later as LuaLua was set free down the left and he cut inside and curled a precise shot into the far corner from the angle of the penalty area.
The Seasiders threatened to run away with it, looking dangerous every time they came forward, but Wednesday responded in the only way they know - an aerial assault - and it almost paid dividends just after the half-hour as Rob Jones tested Gilks with a powerful header from Chris Sedgwick's corner.
The half-time interval did little to disrupt Blackpool's attacking prowess as they extended their lead further in the 53rd minute with the goal of the evening.
Wednesday lost possession and Phillips' cheeky back-heel set Sylvestre free and he advanced into the area and bent a sublime effort into the top corner from 16 yards.
Phillips should have made it 11 in 10 games with 18 minutes remaining as the visitors continued to boss, but when he burst through the Wednesday defence he put his shot the wrong side of the post.
Wednesday did offer some late excitement to their fans as Lowe and Julian Bennett shot wide.
Nevertheless, it was a comfortable evening for Holloway's side, who gain revenge for their first-round Carling Cup exit here in August.