After exiting the city, SR 101 heads northeast through mostly farmland with some patches of woodlands and residential clusters.

[2] Soon after entering Sandusky County, SR 101 makes a left turn to head due north towards the city of Clyde.

The highway passes over the Ohio Turnpike (Interstates 80 and 90) without an interchange and intersects SR 412 at its eastern terminus.

At first, SR 101 deviates from its northeasterly bearing and travels more northerly before curving to due east following the southern border of Castalia.

About one and a quarter miles (2.0 km) northeast of the interchange, just before reaching the Sandusky city limits, SR 101 makes a sharp reverse curve towards the north passing through a light industrial area of western Sandusky before reaching an intersection with US 6.

[1][2] After the aforementioned intersection, US 6 and SR 101 pass over a Norfolk Southern railroad on an overpass and curve to the northeast to travel along Tiffin Avenue.

[6][7] Near the southern city limits of Sandusky, SR 101 formerly traveled on a straight line along Tiffin Avenue where it began a concurrency with US 6 at Venice Road and Sanford Street.