The Bees striker took his season tally to 15 with the treble, a week after his strike partner, Jordan Rhodes, grabbed a half-hour hat-trick against Shrewsbury Town.
Rhodes created the first midway through the first period when he turned brilliantly 30 yards out and slipped the ball through, MacDonald outmuscled Shaun Kelly and toe-poked it under Chester keeper John Danby.
Sam Wood was the architect for the second when he robbed James Owen on the edge of the Chester box and rolled the ball across, MacDonald controlled it and slotted home.
By half-time he had a hat-trick when Brentford were awarded a penalty after Anthony Barry felled Rhodes.
MacDonald stepped up to smash the ball straight down the middle and into the roof of the net.
Brentford were rampant at that point and could have handed Chester an even bigger beating.
Alan Bennett headed against the crossbar, Marcus Bean saw a low shot pushed out by Danby and Rhodes fired narrowly wide from 20 yards.
Nathan Elder had a shot blocked after a nice turn and Rhodes also saw a Chester body get in the way of a goalbound effort, as Brentford threatened to run riot.
Bean headed narrowly over and Wood saw an effort cleared off the line by Kevin Roberts after he shot from a tight angle when he rounded Danby.
Chester offered very little and Bees goalkeeper Ben Hamer did not have a save to make.
Wood cleared a weak Roberts effort off the line late in the first half and Paul Rutherford saw a header deflected wide, but apart from long-range efforts by Jay Harris and Barry the visitors barely got into Brentford's half.