Van Buren was located on a high bluff on the river's west bank.[2] It was named for Martin Van Buren. North of Van Buren was Frog Level Swamp.[3]
Before Fulton was made the county seat in 1837, private homes and stores were used to conduct government business, including the store house of Elisha Thomas at Van Buren.[4][5]
Winfield Walker, a nephew of Winfield Scott, settled in Van Buren in 1838, and became a merchant.[2]
By 1840, Van Buren was the largest town in Itawamba County, and had a busy river port.[5] The populations of both Fulton and Van Buren grew with settlers through the 1840s, and both had blacksmith shops, doctor's offices, stores, and lawyer's offices.[4] A post office operated under the name Van Buren from 1839 to 1867.[6]
The completion of the Mobile and Ohio Railroad west of Van Buren in the late 1850s caused river traffic to diminish;[5] the railway "ruined it and the old site is now under cultivation".[2]