McDonald, who was the club's matchwinning hero when they shocked Everton in the FA Cup third round, struck twice before half time to see off high-flying Carlisle.
The visitors are in a terrible run of form on their travels, losing five in a row without even managing a goal.
Oldham took full advantage and could have at least doubled their tally if their finishing had been sharper.
Carlisle Manager John Ward was refusing to accept excuses and said: "We were abysmal, woeful, call it what you want but the best team won."
Oldham were on top from the start despite losing striker Lee Hughes to an early injury on his return from suspension.
They were also without top scorer Craig Davies but took the lead on 20 minutes as Chris Taylor passed to McDonald, whose shot from 12 yards took a deflection and flew over the head of keeper Keiren Westwood.
Scott Dobie had an angled shot saved in a rare moment of promise for Carlisle, but they were two down before the break as Neal Eardley crossed from the right and McDonald escaped his marker to send home a glancing header from the edge of the six-yard box.
There was little change after half-time, with McDonald almost grabbing a hat trick when he burst on to a neat touch from young sub striker Lewis Alessandra before firing just wide.
The outstanding Taylor sent in a teasing cross which Dean Smalley only just failed to convert and then Taylor was unlucky not to get on the scoresheet with a curling shot which Westwood turned away superbly.
Carlisle could not escape their own half and have two more escapes when Smalley and Stefan Stam both missed chances in the last five minutes.