A double from star striker Andre Gray saw Luton open a six-point gap at the top of the Conference Premier table.
It was the Hatters' 11th consecutive away game unbeaten, a club record, and their 21st league match without defeat.
Gray took just nine minutes to net his 18th of the campaign when he found the top corner from 12 yards.
The hosts levelled before the break when Danny Andrew let fly from 20 yards, but Gray grabbed his second with eight minutes remaining.
VIEW FROM THE DRESSING ROOM
Luton Town boss John Still told BBC Three Counties Radio:
"It was tough, it really was tough, but tough's great sometimes when your back's against the wall.
"Sometimes you've got to come away, dig in and work your socks off.
"You just need that winning mentality and when it got tough, the mentality was a winning mentality."
Macclesfield Town 01 Taylor 26 Halls 03 Andrew 12 Williams 02 Connor 23 Whitaker 25 Kay (Rowe - 87' ) 07 Mackreth 19 Boden (Lewis - 77' ) 09 Holroyd 11 Winn (Fairhurst - 65' Booked ) Substitutes 27 Pilkington 15 Lewis 24 Rowe 08 Fairhurst 06 Turnbull Luton Town 01 Tyler 11 Howells 25 Henry 02 Franks 05 McNulty 43 Ruddock Mpanzu 12 Griffiths 19 McGeehan 21 Guttridge 27 Gray (Lawless - 88' ) 26 Benson Booked Substitutes 07 Lawless 13 Cullen 16 Justham 23 Robinson 06 Charles
Ref: Karl Evans