About 1733 French soldier, Jean D. Girardot, established a trading post in a remote region populated by more than 20 Native American tribes. Girardot chose a promontory rock overlooking the Mississippi River as the site for his trading post. Trappers and River Travelers soon discovered this welcome bit of civilization carved out of the vast forest. They called the place "Cape Girardot."

The man credited with founding Cape Girardeau was French-Canadian Louis Lorimier. Lorimier came to the area from Ohio in 1793. Commissioned by the Spanish Governor General to establish a military post from which to trade with the Native Americans. He welcomed many settlers and even Lewis and Clark on their way to St. Louis for their journey into the unknown West.

With the arrival of the Steamboat in 1835, Cape Girardeau became a river Boom Town. It was the busiest port between St. Louis and Memphis. Until the Civil War, the Riverfront bustled with activity as a commercial center and as an inviting port of debarkation for steamboat passengers.

During the Civil War, Cape Girardeau was occupied by Union forces who built four forts to protect the city and river. For a brief period in 1863, General Ulysses S. Grant set up headquarters in Cape Girardeau.

Today, Cape Girardeau is a regional hub for Education, Commerce, and Medical Care. Although the city's population is around 39,000 people, it is estimated that as many as 90,000 come to Cape Girardeau daily to work, shop, go to school, or visit.

The Bill Emerson Memorial Bridge, officially opened in December 2003, carries 26,000 cars in and out of Cape Girardeau every day.