Senior Alisa Dickerson led the Engineers with 17 points, a career-high 14 rebounds and a season-high eight assists. Freshman Sheree Williams also reached double figures with 16 points.
Sarah Condra led Franklin with 18 points, and Krista Beaman added 10. Franklin dropped to 20-2 on the season and 13-2 in conference play with the loss.
Rose-Hulman earned its first victory over a nationally ranked team since topping No. 22 Trinity 53-51 on Jan. 27, 2006.
Sophomore Kelsey Ploof and sophomore Heather Finnell scored eight points each for the Engineers. Freshman Grace Gibbs also scored six points with 10 rebounds.
Rose-Hulman shot 62% from the field in the first half to jump out to a 32-20 lead at the break. The Engineers turned a 10-8 lead into a 21-10 advantage with an 11-2 run over six minutes to gain control of the first half.
Franklin showcased its national ranking with a strong charge in the second half. The Engineers led by 11 on three occasions, before eight straight points from the Grizzlies cut Rose-Hulman's lead to 47-44 with 4:01 remaining.
Finnell added a jumper and Williams buried two free throws to push the margin to 51-44 at the 3:00 mark. Franklin rallied to within four points at 55-51 on two free throws by Krista Beaman with 1:08 remaining.
Williams hit two more free throws at the 50-second mark to give Rose-Hulman a 57-51 edge, and Kasey Dollins hit one of two free throws to bring Franklin within 57-52. Freshman Emily Fuhs added the Engineers final two points on a pair of foul shots at the 21-second mark.
Rose-Hulman improved to 7-15 overall and 5-10 in conference play, while Franklin stands 20-2 and 13-2 in league games. The Fightin' Engineers return to action on Saturday in the team's annual Breast Cancer Awareness Game against Defiance.