MILE 223: EVANSVILLE, IND. The luck of Angel Mounds, where 1,000 people lived between 1050 and 1400, is that it escaped extreme looting. Some of the millions of artifacts that have been uncovered there  including graceful reddish-brown painted pottery and delicate earrings and nose rings made of bone  are on display in the large museum. I was fascinated by a replica of Kneeling Man, an eight-inch-tall figurine carved in the translucent yellow mineral fluorite, unearthed from the site’s temple mound. Outside, as you walk the area and gaze at the large mounds, beneath your feet are the buried remains of a town that thrived for about 400 years.

MILE 336: LOUISVILLE Back on I-164 north and then I-64 east, drive to another encounter with the wide, winding Ohio, over which canoes carried cargo from settlement to settlement for hundreds, perhaps thousands of years before Europeans arrived. See it up close at Louisville Waterfront Park. From I-64, take the Ninth Street exit and turn left on Market Street. Make another left on Brook Street, which dead-ends at Witherspoon Street and the park. You’ll find walking paths, an adventure playground for children and the Belle of Louisville, the oldest operating steamboat in the nation, which offers a two-hour sightseeing tour. Eat aboard the boat or on land; Joe’s Crab Shack and Tumbleweeds, a Mexican Restaurant, are both in the park.

MILE 436: CINCINNATI Drive another 90 minutes to Cincinnati and find your way to the charming Clifton Gaslight District in the northwest part of the city, a few miles off I-75 south (exit at Hopple Street). A good stop for the night is the Clifton House, a 1900 mansion a few blocks’ walk from lively Ludlow Street with its coffeehouses, restaurants and bars. Cincinnati, like St. Louis, had ancient earthworks that were described in the 19th century, but as in St. Louis, the mounds were flattened long before anyone thought to explore their meaning. When the sun has risen again, set out to the east on Route 32 (take Exit 63B from Cincinnati’s beltway, I-275). Near the tiny town of Peebles, Ohio, turn northwest on State Route 73.

MILE 506: SERPENT MOUND This effigy mound, an enormous earthen sculpture of a snake, is nothing short of astonishing. Walking the footpath that circumnavigates the undulating body or gazing down from the 35-foot platform, it’s hard to wrap your head around this ancient accomplishment. The serpent measures 1,348 feet long, 10 to 15 feet wide and roughly 3 feet high. It is the largest earthen effigy in North America, constructed around 1070. “It’s not an art project built by a bunch of bored people,” said Keith Bengtson, the site manager. “It has a very specific design and intent.” The serpent was documented by surveyors in the mid-19th century, but it was not until the late 1980s that scholars realized its astronomical purpose: its head and coils are aligned to mark the solstices and equinoxes. During the summer solstice, the setting sun descends in perfect alignment with the snake’s head. Hundreds of visitors now come from around the world each year to watch.

Spend some time in the Serpent Mound Museum and then return to Route 73 and continue east. Turn north on Route 41 and drive to Chillicothe, Ohio.

MILE 556: MOUND CITY Walking from the visitors center at the Hopewell Culture National Historical Park to the Mound City Group’s 2,000-year-old cemetery is magically disorienting. A lush green field of huge curvilinear mounds of varying shapes and sizes conveys the sense of stepping into a page from a high school geometry textbook. In all, 23 mounds are enclosed by a low earthen wall at this site  one of five in this sprawling park. The artifacts found in the mounds help tell the story of the people buried there. The Hopewell must have been traders  they had materials like obsidian from the area of Yellowstone National Park, shells from the Atlantic Ocean and copper from near the Great Lakes. Gifted artisans made beautiful creations like copper parrots, human hand shapes cut from sheets of mica and whimsical clay effigy pipes in the shapes of woodland creatures.

“I hope visitors would take away with them that 2,000 years ago there were people with high levels of artistry and complex spiritual cosmology that lived here,” said Bruce Lombardo, a park ranger. “You don’t have to go to Stonehenge or the pyramids of Egypt." The Midwest has its own ancient mysteries.