From Lincoln City, Highway 101 crosses the Siletz Bay National Wildlife Reserve and continues through Gleneden Beach to Depoe Bay. South of Depoe Bay, Highway 101 rises rapidly over Cape Foulweather. The earlier highway is only open to light traffic and winds its way around the cape considerably farther down. On the south side of Cape Foulweather is the small community of Otter Rock, with a "downtown" consisting of about a block of small businesses next to the Devil's Punchbowl. Between Otter Rock and Yaquina Head, the roadbed shows the instability of the local geology. In some places, the highway has simply been rerouted around places where it had proved impossible to prevent the continued subsidence of the grade.
North of Yaquina Head, Highway 101 enters the city of Newport, junctioning with Highway 20 in the middle of town.