Juan Delgado scored his maiden goal in blue and white but Ozan Tufan’s hat-trick and a late Aaron Connolly goal saw Hull down Wednesday.
The Chilean gave the Owls the lead only for Tufan to level with a first half stoppage time penalty.
Tufan then struck two stunners after the break and Connolly extended the lead before Michael Smith netted right at the last, which proved only a consolation.
The Tigers, with two defeats from two so far, started on the front foot and maintained a high tempo throughout.
Regan Slater picked the pocket of Barry Bannan and Devis Vasquez diverted the skipper’s backpass past the post after the latter motored back to make amends.
The Owls defence was the busier of the two as the opening period progressed but Xisco’s backline coped with the regular Hull raids.
Wednesday relied on the counter - which paid dividends on 35 minutes. Callum Paterson’s quick free kick sent Dominic Iorfa scampering down the right and the defender’s low cross was hammered home by the advancing Delgado.
Back came the home side and the Owls had a let-off when Liam Delap’s cross cum shot deflected off Bambo Diaby and onto the upright.
Hull persisted and got their reward three minutes before the interval. Lee Gregory was adjudged to have led with his arm in the box challenging for a high ball with Jacob Greaves and the referee pointed to the spot.
Up stepped Tufan, whose crisp penalty was well-placed and gave Vasquez no chance.
Wednesday suffered a further blow when Bannan, nursing an earlier knock, failed to reappear for the second half.
And on 58 minutes, the assignment grew even harder when the impressive Tufan took possession 25 yards out and unleashed a curling shot that Vasquez could only watch fly into the top corner.
The Turkish international completed his hat-trick on 70 minutes and all but took matters from the Owls’ reach.
Receiving the ball from Adama Traore a yard inside the area, Tufan looked up to bend another beauty past the despairing Vasquez.
The Tigers struck a fourth with five minutes to go when a loose Michael Ihiekwe backpass left substitute Connolly with the simple task of stroking into an empty net.
And despite Smith coming off the bench to apply a fine finish to a George Byers feed right at the last, it was an afternoon to forget for Wednesday.
Wednesday: Vasquez, Iorfa, Ihiekwe, B Diaby, Famewo, Paterson, Delgado (Fletcher 72), Bannan (Vaulks 46) Bakinson (Byers 62), Windass (Musaba 62), Gregory (Smith 62)