Scott is trying to match Robert Allenby's 2005 accomplishment of winning the Open, Australian Masters and Australian PGA in succession. Scott also won the Masters at Augusta in April.
Scott shot a course record 62 on the first day and followed with a second-round 70. Saturday's round of six birdies and two bogeys moved him to 16-under 200 for the tournament.
McIlroy started the day two shots behind Scott and lost ground with a bogey and double-bogey against five birdies, finishing with a 70. McIlroy is vying for his first victory of the year.
Australians Richard Green, Matthew Jones and Max McCardle shared third place at 8 under, eight shots off the pace.
Scott's round on Saturday means he is now 51 under par for his three tournaments in Australia this year.
"To win my national championship tomorrow and then also win the three events down here is an unbelievable spot to be in," Scott said. "If you'd told me that a month ago, I wouldn't have believed you.
"Before this month started, I hadn't won two tournaments in a row ever. So to have this opportunity is a bit unreal."
Scott said he would sleep easier after holing a six-foot birdie putt on the last hole and then watching McIlroy miss a birdie putt from closer range to increase the Australian's lead.
"One round away and a lot can happen," he said. "(There's) a phenomenon behind me as well so I'm sure he's going to throw plenty at me tomorrow.
"I'm going to have to do a couple of things better than I did today. But as long as the eye stays in with the putter, I should be able to hang on. To finish it off tomorrow would be an incredible way to end the year."
McIlroy said his missed birdie chance on 18 had been costly.
"It was big," he said. "It would have been nice to birdie that to make the gap from four to three."
Jason Day, who partnered with Scott to win the World Cup of golf for Australia last week, had the day's equal-best round of 66 to briefly take the clubhouse lead but eventually that was only good for a tie for 10th.