Continuing on, I-81 begins to follow the Tioughnioga River, a tributary of the Susquehanna, as it bypasses the nearby village of Lisle to the east. While US 11 runs across the base of a valley flanking the river, the freeway proceeds along the valley's eastern edge, overlooking the valley road on its way to the Broome–Cortland county line. Both routes cross the border at points just yards apart, beginning their transition from the Southern Tier region to Central New York. About from the county line, I-81 encounters the village of Marathon, situated inside the river valley at the junction of US 11 and NY 221. The freeway connects to the latter at an interchange just east of the village center before heading northwestward for across a series of moraines in another prolonged rural stretch. Along the way, I-81 passes between the Tuller Hill and Hoxie Gorge state forests, located near Messengerville on the western and eastern sides of the highway, respectively.