Lewis and Clark headed up the river, stopping on July 4, 1804 at Independence Creek, just outside today's Atchison, Kansas. A large Kansa Indian village stood by the bluff in Atchison when the explorers passed through. Their stopping point is at the end of a 10-mile walking/biking trail and has a replica Kansa Indian earth dwelling. The hiking/biking trail leads into downtown Atchison, where an open-air pavilion commemorates the historic 1804 journey. Across the street is the landmark Old Hoof & Horn at the Riverhouse Restaurant, a great stop for a casual lunch or dinner. Atchison is also known as the home of the Atchison, Topeka, and Santa Fe Railroad – the visitor's center is located in the old depot – as well as the birthplace of Amelia Earhart. Earhart's home is one of many significant buildings to tour. Shoppers flock from Kansas, Iowa, Nebraska, and Missouri to get home accessories at Nell Hill's, a home decorating store downtown.

Cross over the river for a scenic drive up Route 59 into St. Joseph, Missouri. Once home to Jesse James and the founding location of the Pony Express, St. Joseph also hosts one of the nation's most unusual museums. The Glore Psychiatric Museum depicts the horrors of mental healthcare through the ages – from chaining patients to cell walls to confining them to cribs covered with slats, even burning them at the stake.

Hit I-29 for a quick drive into Iowa, with a stop for lunch at Stoner Drug Company in Hamburg. Straight out of "Leave It to Beaver," kids toss their unlocked bikes at the front door to scoot in for a soda and ice cream. Slide into a booth, or perch on a red-plastic covered stool for a genuine malt at the marble counter. Sodas are just $1.95, floats $2.50.

Continue north, crossing the river once again into Nebraska City, Nebraska, birthplace of Arbor Day. In the late 1800s, this area was prairie grass, and Stirling Morton built a four-room home where he could see the river 2½ miles away. The newspaper editor began planting trees, foresting the land and establishing windbreaks. Morton's home, expanded by his children into a 21-room mansion by the early 1900s, was given to the state and is now part of Arbor Lodge State Historical Park. Visitors can also tour Arbor Day Farm, sampling apples from the orchard.

Lied Conference Center, a hotel/conference/dining facility with a dramatic Adirondack-style lobby, is a short walk from Arbor Day Farm. A fuelwood energy plant heats and cools the stunning property entirely with wood. The dining room overlooks the orchards, ablaze with color in the fall, and vibrant green in spring and summer. The menu, of course features apple accents, from apple-cider-spiked oatmeal to apple-smoked salmon.

The Missouri River Basin Lewis and Clark Interpretive Trails and Visitors Center opened in 2004, just in time for the 200th anniversary of the journey. The site overlooks the Missouri River, where visitors can wander trails laced with the flora and fauna that Lewis and Clark catalogued. A replica of one of the expedition's keelboats, seen in the IMAX movie about the trip, dominates the visitor's center.