Kerr overcame a bout of lightheadedness at the start and had one of only six rounds under par on the tough Saucon Valley Country Club layout, offsetting four bogeys with five birdies. She stands at 3-under 139.
Creamer, looking for her first Womens Open title and first major, carded a 3-under 68 after an opening 72 and was alone in second at 2-under 140.
Duramed Futures Tour player Jean Reynolds is third after a 72 for a 1-under 141.
Top-ranked Lorena Ochoa struggled to a round of 8-over 79 and stood at 6 over for the championship.
The final two rounds will be spiced with a bit of old and new. Former champion Laura Davies, playing on a special exemption, made the cut, as did 14-year-old amateur Alexis Thompson, who is in contention after a 73 put her at 2 over and tied for eighth.
The focus Friday was back on golf, a marked change after the event was overshadowed all week by a dispute between some LPGA players and commissioner Carolyn Bivens. On Thursday, reports surfaced saying Bivens could be out of her job as early as next week after more than a dozen players signed a letter calling for her resignation.
A day later, the narrow fairways and speedy undulating greens at the Old Course demanded the players attention as the cut line fell at 9 over.
Not feeling her best at the start, Kerr opened with a bogey and four pars. She began feeling better on the 13th ' she started on the back nine ' and hit stride on the 15th through 17th.
Kerr rolled in putts of 9, 3 and 8 feet for her run of birdies and, after a pair of bogeys to open her back nine, made birdie putts of 15 and 12 feet on the way in to maintain the lead.
Creamer is coming off a thumb injury that forced her to miss the last two tournaments but there was no sign the sore thumb is affecting her play at Saucon Valley.
She started the day 1 over, and moved into red numbers after back-to-back birdies at the ninth and 10th. Her round included five birdies, two bogeys and 11 pars, good enough for sole possession of second, her best standing after two rounds in an Open.
Reynolds continued to be the surprise of the event. A two-time winner this year on the Futures Tour ' and its leading money winner ' she hung tough in just her second Womens Open.
Reynolds overcame hitting just nine of 14 fairways to give herself a shot at the championship.
Davies followed an opening 72 with a 75 and is at 5 over, tied for 28th. She won the 1987 Open, beating Ayako Okamoto and JoAnne Carner in an 18-hole playoff for her first professional victory. She has played in every Open since 1986.
The 20-time LPGA winners last victory came in 2001, at the Wegmans Rochester International. She has struggled on tour this year, making the cut in five of 10 tournaments, with her best finish a tie for 33rd at Phoenix in March.
Davies has been inconsistent at the Womens Open, too. She has missed the cut in eight of the last 12 championships and last played the weekend in 2007, when she tied for 32nd. She does have eight top-15 finishes
Thompson made the cut for the first time in three tries, following an even-par 71 with a 2-over 73. But her 2-over 144 score not only made the cut by seven strokes, it left her in contention for the title two years after she became the youngest player ever to qualify for the Womens Open.
Among the players missing the cut were: Se Ri Pak (11 over), 49-year-old Rosie Jones (12 over) and two-time Womens Open champion Meg Mallon (18 over).