The freeway enters Rockingham County, where it crosses the North River and meets SR 257/SR 682 at an interchange, east of the town of Mount Crawford that also provides access to Bridgewater College. From this point, I-81 enters commercial areas as it comes into the independent city of Harrisonburg, and has it first interchange in that city with US 11, at a trumpet interchange. The freeway continues to cross over the Roanoke District's Chesapeake Western Branch rail line, interchange with SR 253 providing access to the downtown area of Harrisonburg and the JMU Convocation Center, before it passes along the southern edge of the campus of James Madison University and reaches an interchange with US 33 that provides another outlet to Skyline Drive and Shenandoah National Park, as well as to the campuses of the Harrisonburg Campus of the American National University and the Eastern Mennonite University. Just after this interchange, I-81 crosses over the Chesapeake Western Branch line again, before leaving Harrisonburg and re-entering Rockingham County prior to reaching another trumpet interchange serving US 11. The freeway heads back into rural surroundings, where it meets another interchange with US 11, providing access to the southern terminus of SR 259 serving the towns of Broadway and Timberville, as well as the Endless Caverns site, in the hamlet of Mauzy. Afterward, I-81 continues northeast to another bi-directional rest area, and then leaves Rockingham County.