The 26-year-old striker, who left Hillsborough in July 2007 after three years with the club, refused to celebrate as he ran on to a David McNamee pass to slot the ball past Lee Grant from eight yards
MacLean, whose last appearance was in August, had been recalled by former Wednesday manager Paul Sturrock to inject some life into his Plymouth side after their 3-1 defeat against Ipswich at the weekend.
Plymouth, 4-0 winners at Home Park three weeks ago, started brightly, Jim Paterson's teasing cross from the left flank cut out by full-back Peter Gilbert, with Paul Gallagher waiting to pounce eight yards out.
The Sheffield side, unbeaten at home and with four consecutive clean sheets at Hillsborough almost found a way through, midfielder Steve Watson steaming into the area, his right-foot strike blocked by Chris Barker.
Francis Jeffers, back in the side after a long-term injury, produced a class shot on the turn, the ball deflecting over the top as Wednesday turned the screw.
Leon Clarke hammered a stinging shot inches wide of the target before winger Jermaine Johnson cut inside, his low strike scooped up on the line by French keeper Romain Larrieu.
Plymouth took the lead in dubious fashion in the 23rd minute, McNamee picking out MacLean who looked distinctly offside as coolly stroked the ball past the advancing Grant.
The rest of the first half saw few clear chances for either side, with the Pilgrims rarely looking like surrendering their lead.
The lively Clarke almost levelled matters in the 60th minute as he barged his way into the area, before he was stopped in his tracks by Craig Cathcart under the nose of the Plymouth keeper.
Johnson had a chance to level matters in the dying seconds after neat work by substitute Deon Burton, but he blasted wide to leave the Owls faithful disappointed.