The 30-year-old posted a fine six-under 67 to lead by a shot from Gwladys Nocera and Malene Jorgenson with Solheim Cup player Charley Hull two strokes further back on three-under.
MacRae's last visit to the National Golf Club in November ended in anguish when she just missed out on promotion to the main Ladies European Tour by one place after the final event of the second-tier circuit.
"It was a bit of a heart breaker because I finished 10th in that event and missed my card by just 40 points," said MacRae, who has limited starts on the main tour this season. "I knew I'd hit a lot of good shots here so that's helped coming back. It's my lowest round as a professional and hopefully I'll have learned from that Access event."
Musselburgh's Vikki Laing opened with a 71, while Sally Watson, beaten in a play-off on the Access Series last weekend, posted a 74. Carly Booth's struggles continued, however, as the two-time tour winner sagged to an 81.