Smithville is one of the older towns in Monroe county. It is located on the Gaines Trace Road which was surveyed by E. P. Gaines in 1807 at the request of President Thomas Jefferson. The land Smithville sits on was owned by Che-lah-cha-chubby, a Chickasaw Indian chief or sub-chief, and a trading post was established in 1820 at the location of what is now the intersection of highway 25 and Hatley-Smithville road. Gaines Trace was a major route for settlers who migrated from the northeast.

On April 27, 2011 at 3:47 P.M CDT an EF5 tornado struck the town. Its winds are estimated to have peaked at 205 miles per hour (330 km/h).[4] 16 people were killed,[5] and 40 people were injured.[4]

Smithville won two 1A football state championships in 1993 and 1998. The school previously vied for the title in 1989, losing to a Mt. Olive (MS) team quarterbacked by future NFL great Steve McNair. The Smithville High School softball team has won the 1A state championship in 2008, 2011, and 2012.[8] The Smithville High School Band has won two state Marching Championships.