The game kicked off at pace in Sanquhar, with both teams going for it. Moray Ferguson opened the scoring for the Young Blues just before the half hour mark.
But Nithsdale striker Sean Mckenzie soon equalised before the break.
Within seven minutes of the restart, the visitors re-gained the lead as Ferguson notched his brace.
Jake Ellis added a third before Harry Mitchell netted a fourth to seal victory.
The Reserves now sit five points clear at top of league. Dalbeattie and Lochar can pass them if they win games in hand, but all teams still have tough fixtures left to play.
Over in Lockerbie, Newton Stewart came away 5-1 winners in their against Mids.
The Creesiders took the lead early when Robbie Murray smashed an unstoppable first time strike into the roof of the net.
But they suffered a double blow midway through the half when Robbie Thomson and Euan Drysdale both left the field injured.
The Mids striker soon headed home to level the match.
However, within 60 seconds the visitors were back in front when Marc Whyte sent through a measured ball to Craig McCulloch. And the pacey winger raced through before sweeping his shot past the advancing keeper.
Two minutes Jack Marshall calmly picked his spot before stroking the ball into the net.
The visitors suffered a further setback five minutes from the break when Robert Hughan also had to exit the field with injury.
However, Harry Hay and Whyte both extended the advantage in the second half.
Elsewhere, Wigtown and Bladnoch were on the wrong end of a 8-0 hammering as they hosted Lochar Thistle at Blairmount Park.
