The American frontier was pushing past the Mississippi River in the early 1800s. Lewis and Clark's expedition to the Pacific had started a migration west to the Rockies and beyond.

As the frontier moved, civilization filled the void it left behind. Moses D. Bates was one of the men who entered the area, and in 1819 he went out looking to start a river town. He chose Hannibal's current location and named the town after Hannibal Creek, present day Bear Creek. Bates built the town's first building, a cabin located near the corner of North Main and Bird streets.

The town grew modestly in the beginning. Hannibal's population was only 30 people in 1830. The Mississippi helped the economy grow in the middle of the 19th century and Hannibal became chartered as a city in 1845. James Brady was the town's first mayor and the city grew to 2,020 people by 1850.

River access, abundant timber and fertile farmland combined with an influx of settlers and immigrants to create a thriving economy. Early industries included pork packing, soap and candle making, milling of lumber, rope making and tanning. The river also brought steamboats to Hannibal. By the mid-1800s, more than 1,000 were landing each year.

The California Gold Rush in 1849 had an effect on Hannibal and the surrounding area. More than 200 men went to seek their fortunes and most returned with some measure of financial success. The money was poured into the local economy and Hannibal continued to grow.

The railroad industry also helped contribute to Hannibal's growth. The first railroad to cross Missouri, the Hannibal and St. Joseph Railroad, was completed in 1859.

When the Civil War broke out in 1861, most of the town favored the Confederate cause, but the town was occupied by Union soldiers for the entire war. During the war years, the railroad and the river helped to make Hannibal the second-largest city in the state and the third-leading commercial center.

As the steamboat, lumber and railroad industries diminished in the early 1900s, the town's prominence tapered off as well. The town also suffered during the Great Depression and Hannibal's population began to decline.

However, despite the hard times, a diverse group of industries carried Hannibal through the middle part of the 20th century. Today, the town continues to boast a wide variety of industry. Everything from agricultural chemicals to automotive equipment is produced in Hannibal. These industries, coupled with tourism, form the base of Hannibal's economy.