The victory at the Riverside Stadium was watched by a crowd of 28,229 - Boro's biggest attendance for over three years - and moved the hosts above Crystal Palace at the top of the table.
It was a seventh win in eight outings for Tony Mowbray's ominous outfit, with struggling Wednesday losing for the fifth time on the road since promotion.
In a bid to put vocal support behind such a fine run of form, ticket prices were slashed in half ahead of the game, attracting the largest crowd at the Riverside since May 2009 - Boro's final month in the Premier League.
The Boro fans had a goal to cheer after just 13 minutes as right-back Justin Hoyte opened the scoring. Emmanuel Ledesma played a beautifully weighted pass down the right channel, and Hoyte was able to run onto the ball in the box and strike a firm shot into the roof of the net.
Shortly after the half hour, Owls goalkeeper Chris Kirkland denied Josh McEachran from close range after a fine jinking run from the on-loan Chelsea midfielder.
Miguel Llera put a shot wide of Jason Steele's goal on 40 minutes following a corner at the other end, as Boro maintained their half-time advantage.
Three minutes after the restart, Wednesday enjoyed a touch of good fortune as Gary Madine equalised. Replays showed the Owls striker was offside when Michail Antonio chested the ball down in the box from Jay Bothroyd's long pass, but he finished well and the goal was given - despite Mowbray's protests at the fourth official.
However, on the hour mark, the visitors gave the ball away in their own half, and a classy turn and pass by Ledesma resulted in Scott McDonald running through into the box and getting a touch, allowing Ishmael Miller to tap home and restore Boro's lead.
Miller was later subbed off for Lukas Jutkiewicz, and the replacement headed home at the near post from a Grant Leadbitter corner on 76 minutes to put the seal on the victory.
Madine threatened to set up a tense finale with his swerving effort in the final phases, but Steele was more than equal to the task and Boro had earned their sixth home victory of the season.