The Blue Devils, chasing their fourth national title, blitzed the field with a 1-under-par 287 to go from a three-shot deficit to Arizona State at the start of the round to a 13-stroke lead over Southern California at the finish.
That performance mirrored what they did a year ago when they went 6-under in the third round at Sunriver, Ore., to take an eight-shot lead. They eventually held off UCLA by five strokes to take the title.
Duke was at 12-over 876 through 54 holes at Ohio State's reconstructed Scarlet Course.
Freshman Amanda Blumenherst, ranked No. 1 in the nation during the regular season, led the way with a 70 that matched the low round of the day. Elizabeth Janangelo had a 71 and Jennie Lee a 72. Jennifer Pandolfi shot a 74 and 2005 medalist Anna Grzebien parred the first 16 holes before closing with two bogeys to also post a 74.
USC totaled 298 strokes and was at 889, followed by Pepperdine (894), and Purdue and Arizona State (896).
Windy conditions turned club selection into so much guesswork. Shortly after play was completed, a large thunderstorm swept through the region.
Vargas, a junior from Colombia, has led the individual race from the beginning, shooting a tournament-best 4-under 68 in the opening round and following that with a 71.
She got off to a rocky start in the third round, bogeying five of the first 10 holes. Her 75 included seven bogeys and four birdies and pared what was a four-shot lead to begin the day to three strokes.
Vargas stands at 2-under 214 heading into the final round. Tied for second are Florida's Sandra Gal (71), Duke's Lee, USC's Schreefel (70) and Stanford's Jennifer Tangtiphaiboontana (72) at 1-over 217.
A year ago, Vargas was in contention for medalist honors through the first two rounds, then slumped to shoot 83 and 75 and finished in a tie for 55th, 16 shots behind Grzebien.
Da Sol Chung of UNLV was alone in sixth at 218 after joining Schreefel and Blumenherst with a 70.
Janangelo shared seventh with Purdue's Maria Hernandez (71) at 219, with Blumenherst, Florida's Tiffany Chudy (76) and UCLA's Amie Cochran (71) next at 220.
Duke's previous NCAA titles came in 1999, 2002 and 2005.
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