Second half goals from Rob Jones and Reda Johnson cemented Wednesday's best home start to a season for over half a century.
The Owls posted what was an ultimately comfortable win over Colchester, who despite a bright start headed home to Essex with nothing to show from their trip to Hillsborough.
The victory was Wednesday's seventh on the spin in S6 this term.
Colchester came to Hillsborough in the midst of a productive run of form and the start to the game mirrored the visitors' confidence.
Michail Antonio sent a teasing cross into the heart of the danger zone inside two minutes and the onrushing Kemal Izzet glanced a diving header wide when he might have done better.
The Owls then survived a penalty claim when Andy Bond's flick in the area was halted by Jose Semedo but the referee ruled any contact on the arm as accidental.
After a far from convincing start, Wednesday grew into the game and Gary Madine fired the hosts' first shot on goal that was comfortably gathered by Ben Williams just after the 15-minute mark
Chris Lines sent a curling drive narrowly over the crossbar five minutes later as the Owls began to dominate.
And Wednesday thought they had the lead on 30 minutes when Madine converted Ben Marshall's long throw but the goal was disallowed for an infringement.
Lines brought a fine save from Williams before the interval, Madine had a fierce effort charged down and Wednesday went down the tunnel having edged the first half.
Gary Megson introduced Jermaine Johnson for the resumption, with James O'Connor making way for the flying winger.
But it was Marshall on the other flank that caused more problems, one run in particular bamboozling two defenders and forcing Williams into a diving save.
The resulting corner triggered a goalmouth scramble that saw Madine strike the crossbar.
The Owls kept the pressure on and were rewarded on the hour. Madine drilled a powerful drive that Williams found too hot to handle and Jones was on hand to smash home the rebound.
O'Grady almost doubled the lead moments after the restart but Williams dived full stretch to parry the striker's shot to safety.
The U's rallied briefly to forge a way back into the game but promptly fell two goals behind.
Lines' free kick found Madine, whose turn and shot across goal landed kindly at the feet of Reda Johnson, who buried emphatically past Williams from close range.
It was all Wednesday in the closing stages and Jermaine Johnson should have further extended the lead but shot wide with the goal at his mercy.
All in all, though, another productive afternoon at Hillsborough for the Owls, who face a long trip north of their own on Tuesday but will travel to Carlisle in good heart and just two places from the summit of the League 1 table.
Owls: Bywater, Buxton, Batth, Jones, R Johnson, O'Connor (J Johnson 46), Semedo, Marshall (Palmer 86), Lines, O'Grady (Lowe 84), Madine
Unused substitutes: O'Donnell, Bennett
Colchester: Williams, Heath, Izzett (O'Toole 77), Antonio (Gillespie 69), Bond, Odejayi, Henderson, Eastman, Wilson (White 86), Wordsworth, Coker
Unused substitutes: James, Duguid