The diminutive forward pounced in the 21st minute after a slip-up by Brighton goalkeeper Casper Ankergren at the Riverside.
Under no pressure, Ankergren spilled a cross and McDonald converted from close range at the second attempt.
The result put Middlesbrough within two points of second-placed West Ham United, with the top two teams at season's end being elevated to the lucrative English Premier League.
In the Netherlands, Brett Holman set up the opening two goals for league leader AZ Alkmaar in its 4-0 romp over De Graafschap.
In the English top flight, Tim Cahill's Everton succumbed to a stunning volley from superstar Robin van Persie as Arsenal celebrated its 125th anniversary with a 1-0 win in north London.
Mark Schwarzer's Fulham lost 2-0 at Swansea City while uncapped Australian midfielder Chris Herd's Aston Villa enjoyed a 2-1 win at beleaguered Bolton Wanderers.
In the German first division, former Adelaide United forward Matthew Leckie came off the bench in the 70th minute in Borussia Monchengladbach's 1-0 loss at Augsburg.