Interstate 155 begins at a near-full cloverleaf interchange with I-55 in Pemiscot County, Missouri, on the edge of Hayti, where US 412 continues as a four-lane divided highway to the northwest.

Passing through additional farmland, the Interstate crosses the Obion River a few miles later and has an interchange with SR 182 a short distance beyond south of the Lenox community.

By the late 1930s, Missouri and Tennessee were two of the few remaining bordering states in the country which were not directly connected by road or rail, and a bridge across the river began to be proposed.

[3] Caruthersville newspaper The Republican reportedly suggested a bridge be constructed in the area in 1936 or 1937, and by early August 1939, a group of local citizens began promoting the idea.

[6] On September 15 of that year, the Caruthersville and Dyersburg chambers of commerce held a meeting and established the "Hands Across the River Committee" to promote the project.

After this system was authorized by the Federal-Aid Highway Act of 1956, officials in Missouri, Tennessee, Kentucky, and Illinois began an effort to improve connectivity between the four states.

On January 7, 1960, Tennessee officials submitted a letter to the Bureau of Public Roads (BPR), predecessor agency to the Federal Highway Administration (FHWA), for the approval of a 63-mile (101 km) between Hayti and Jackson.

[15][16][17] This proposal was echoed by the bridge commission in a meeting with BPR administrator Rex Marion Whitton on May 25, 1961, but was reportedly not considered since the federal government had yet to determine how many miles they would be able to add to the Interstate system.

[6][18] On January 30, 1962, Governors John M. Dalton of Missouri and Buford Ellington of Tennessee jointly submitted an application to the BPR for the new Interstate.

[19][20] On September 17, 1963, the governors of the four states met with President John F. Kennedy where they reached an agreement on the alignment for the I-24 extension and endorsed the routing for the Hayti-to-Jackson Interstate Highway.

[33] This project required the construction of an artificial levee within the Mississippi River flood plain, which proved to be one of the most difficult jobs undertaken by TDOT.

On June 22, 1980, the American Association of State Highway and Transportation Officials established US 412 along I-155 as part of a route between Jackson and Walnut Ridge, Arkansas.

An extension of Interstate 69 through Tennessee was proposed under the 1991 Intermodal Surface Transportation Efficiency Act (ISTEA) as part of a corridor to facilitate trade between Canada and Mexico.