For the second successive match skipper Gary O'Neil was not included in the Boro squad.
O'Neil has been one of Middlesbrough's most influential players this season, but his absence is for financial reasons. As part of the transfer agreement with Portsmouth four years ago, Boro agreed to pay an extra £1million pound if the midfielder made 100 first-team appearances.
O'Neil is on the 99 mark and Middlesbrough are reluctant to pay out the seven-figure fee at this stage in the season, especially as his contract runs out at the end of the season.
Relegation fighting Wednesday made a late change with Jermaine Johnson taking over from Leon Clarke, who was named in the original squad.
There was no official announcement over Clarke's absence though he could have been injured in the warm-up.
If Boro had anticipated a defensive Wednesday approach with quick counterattacks, they were in for a surprise at the start.
Wednesday put the accent on attack in a bid to get out of the relegation zone and received tremendous vocal backing from the 2,442 visiting fans in the 19,932 crowd.
Bradley Jones was called into action on several occasions, with the Boro keeper the target off the boo-boy' early in the season, but he has redeemed himself in the eyes of the home fans.
Wednesday keeper Lee Grant went full length to save a 30-yard shot by Leroy Lita.
Middlesbrough went ahead five minutes before half-time when former Celtic striker McDonald scored with a deflected shot that gave Grant no chance.
Wednesday went in search of an equaliser after the break and Luke Varney was unlucky when he headed on to the bar from a Darren Potter corner.
Boro hit back and Grant brilliant saved a 25-yard Rhys Williams shot. Both teams played with competitive spirit and the result was in the balance until the final whistle although there was a lack of attacking flare.
Wednesday face an anxious finale with the home derby against Sheffield United next Saturday of vital importance, to be followed by games against Cardiff City and Crystal Palace.