^Looking east from the intersection with Ohio 193 west of Andover, October 2022.
In Ohio, US Route 6 spans the full width of the northern part of the state. In northwestern Ohio and northeastern Ohio, US Route 6 is the second-most northerly US Highway in Ohio, after US Route 20. However, in north-central Ohio, US Route 6 is the northernmost, staying north of US Route 20. From Fremont to Cleveland, US Route 6 stays alongside the waters of Lake Erie. But US Route 6 tends to stay straight east-west outside of that range. US Route 6 enters Ohio between Butler, Indiana, and Edgerton, Ohio. It stays south of Toledo, running through Napoleon and Bowling Green, instead. At Fremont, US Route 6 turns northeasterly to meet the lakeside, serving Sandusky and Huron. From Huron to Cleveland, US Route 6 hugs right along Lake Erie's southern shore. Beyond Cleveland, US Route 6 heads due east as the shoreline traces northeasterly. At Andover, US Route 6 jumps northerly to a different alignment headed east for the Pennsylvania border, to get around the Pymatuning Reservoir (even though Ohio Route 85 continues straight easterly over the Reservoir, anyway).