Hillsboro (pop. 6,605), 60 miles east of Cincinnati and 40 miles west of Chillicothe, is the biggest and busiest town along the way. Besides the Greek Revival landmark Highland County Courthouse, second oldest in Ohio, Hillsboro has a unique alcohol-related history: During Christmas in 1873, the town’s 13 saloons were closed down by one of the country’s earliest temperance movements, and more recently, late great country singer Johnny “Take This Job and Shove It” Paycheck did time in prison for shooting a man in Hillsboro’s North High Saloon. (Even more recently, that saloon was torn down to make way for a new city office building.)
Across southwestern Ohio, US-50 winds past whitewashed farmhouses and broad cornfields flanked by low hills. The region also holds two fascinating remnants of the Mound Builder people who once lived here. Just west of the sleepy village of Bainbridge, heading 20 miles south onto Hwy-41 (or following Hwy-73 south from Hillsboro) brings you to the Serpent Mound (800/752-2757, daily 9am-dusk, museum daily 10am-4pm Apr.-Oct., Sat.-Sun. Mar. and Nov.-Dec., $8 per car), which stretches in seven sinuous curves alongside a creek for nearly a quarter mile. There’s a small museum on the site. To see the snake-shaped earthworks—the largest and finest effigy mound in the country—visitors climb up a turn-of-the-20th-century vintage lookout tower.
Another of these prehistoric sites, the Seip Earthworks, 2 miles east of Bainbridge and 14 miles west of Chillicothe, is over 200 feet long and 30 feet tall, surrounded by 10 acres of pasture. To prevent early farmers from plowing them into oblivion in the 1880s, many of these evocative monuments were purchased and preserved through the efforts of Harvard University archaeologists. Harvard owned the land for many years and later donated the sites to the state of Ohio.