Stepping well from box five, the fawn dog (pictured winning his heat last week) had too much burn in the run to the line on the first occasion, crossing to the fence around the first turn and kicking clear.
Hot on his heels down the back was Jesaulenko (box eight), but despite the Terri Morris-trained dog's best efforts, he couldn't get to the leader in the run to the line, finishing three quarters of a length off Ando's Mac in 29.48.
South Australian star Worm Burner (box two) produced a strong run from midfield to grab third, while favourite Zambora Brockie was never a winning chance after being shuffled back in the early stages.
Trained in the Hunter Valley by Jason Mackay, Ando's Mac is the first NSW greyhound to win the Melbourne Cup since Go Wild Teddy scored back in 2000.
Owned by Luke Anderson and his partner Michaele Alderdice, Ando's Mac has now won 16 of his 29 career starts, with his resume also boasting a dominant victory in the Group 1 Vic Peters Classic at Wentworth Park last month.
A June 2014 whelp, the son of El Grand Senor and Brook's Doll has now won a whopping $556,386 in prize money earnings, a figure which places him in 15th spot on the all time prize money earner's list.