At this time, the route was incorporated into the Interstate Highway System as I-410 and was intended as part of a northern bypass of I-10 utilizing the existing Mississippi River Bridge on US 190.

[3][4][5] I-110 briefly passes through the Spanish Town neighborhood as it descends to grade and bends sharply due east in front of the Governor's Mansion.

After curving back to the north, I-110 elevates again and travels for three miles (4.8 km) through a residential neighborhood located just east of a large industrial area.

[3][4][5] I-110 then engages into a stack interchange (exit 5B) with the concurrent US 61/US 190 (Airline Highway), which sweeps around the northeast side of town and crosses the Mississippi River en route to Opelousas.

Immediately to the north, exit 6 to LA 408 (Harding Boulevard) provides access to Baton Rouge Metropolitan Airport and Southern University.

Curving westward, I-110 skirts the Scotlandville area and has a half diamond interchange with LA 19 at exit 8A, connecting with the nearby suburb of Baker.

[9] Traffic was fed onto the expressway from the downtown area via the one-way couplet of North 9th and 10th Streets, a continuation of the divided thoroughfare of East Boulevard.

[9][12] The connections to I-10 were made when the adjoining sections of that highway were completed eastbound to Perkins Road in September 1964[13] and westbound across the Mississippi River in April 1968.

[14] I-410 was intended as a northern beltway extending from I-10 west of Port Allen, crossing the Mississippi River via the existing Huey P. Long Bridge on US 190, and then traveling along the present route of I-110 southward to rejoin I-10.

[24] In 1991, three separate parties advocated for the naming of a Baton Rouge-area thoroughfare after civil rights activist, Martin Luther King Jr.

[25] The proposal also met with strong opposition from the outside, including Louisiana House of Representatives member and then-gubernatorial candidate David Duke, who opposed naming any street for King, stating that his "reputation as a womanizer means the honor is an insult to women and family life.