Start your Mississippi River tour in the historic town of Galena, a bustling hub for steamboats and lead mining during the 1800s. Take a tour of the area with Galena Trolley Tours. Docents provide the inside scoop on local landmarks and the historic presidential home of Ulysses S. Grant. Have lunch at Fried Green Tomatoes, an upscale Italian restaurant that was once a leather shop owned by Grant's family. Then hop on the Stagecoach Trail that leads into the beautiful surrounding countryside and check out the award-winning Galena Cellars Vineyard & Winery. Tour the winery and vineyard, learn how to taste wine and sample the latest vintages (accompanied by local cheeses). For dinner, sit back with a pint of Guinness and watch the authentic Irish entertainment at Frank O'Dowd's Irish Pub, a lively nightspot in The Irish Cottage Boutique Hotel that serves tasty pub grub. Afterwards, spend the night in the historic DeSoto House Hotel, the beautiful Chestnut Mountain Resort, or at one of the many quaint local bed and breakfasts.

Begin the day shopping on Galena's charming Main Street, noted for its 19th-century buildings that today house modern shops, galleries and restaurants. Then head to Moline, the hometown of farming hero John Deere. Learn about his legacy at the John Deere Pavilion, a striking complex on John Deere Commons housing vintage and modern Deere equipment along with agricultural exhibits. The next-door John Deere Store carries everything from t-shirts to collectibles bearing the famed leaping deer logo. Close by is the John Deere Collectors Center, where true Deere fans will revel in watching antique machines being restored. Take a break with a narrated lunch cruise (featuring live entertainment) on the Mississippi River aboard the Celebration Belle, an 800-passenger riverboat that docks in Moline. Then head to Rock Island and the Quad City Botanical Center, which houses tropical plants and a 14-foot waterfall. In the middle of the Mississippi on its own island is the U.S. Army's Rock Island Arsenal, with sites such as the Rock Island Arsenal Museum and a Confederate cemetery that are open to the public. In the evening, head to Rock Island's The District, home to several art galleries, nightspots and restaurants. Afterwards, try your luck at the table games or slots at Jumer's Casino Rock Island, a three-deck riverboat right on the Mississippi.

Drive to Nauvoo, a river town that's rich in Mormon history. Visit the Joseph Smith Historic Site, which traces the Latter-Day Saints movement in 1840s Nauvoo. Join a guided walk or take a horse-drawn carriage ride through the site to see such Mormon landmarks as the Brigham Young Home and the Smith Homestead. Have lunch at the nearby Thyme & Seasons Restaurant. Then stop by Baxter's Vineyards & Winery, Illinois' oldest winery, for a taste of its new Apple Smack sweet apple wine. Afterwards, travel the scenic Great River Road. Complete your Mississippi River experience in Alton at the National Great Rivers Museum, located on the Meeting of the Great Rivers National Scenic Byway. The museum illustrates the history and important transportation role of the Mississippi through interactive exhibits and displays. The museum is located at the Melvin Price Locks & Dam, which is open to the public for guided tours. Have lunch at Castelli's Moonlight Restaurant, an Alton dining tradition for more than 60 years. Afterwards, make tracks to the Lewis & Clark Interpretive Center in nearby Hartford. See a replica of Camp River Dubois and a full-scale model of the keelboat that the explorers used to set out on their journey from Illinois.