Combined, I-440 and Briley Parkway, a controlled-access segment of State Route 155 (SR 155), form a noncontiguous inner beltway around downtown Nashville.

About 1.5 miles (2.4 km) later, the Interstate turns southeast and reaches a partial cloverleaf interchange (parclo) with US 70S (West End Avenue), which is indirectly accessible from the eastbound lanes via a connector road.

Turning further southeast and passing near Centennial Park and Vanderbilt University, the highway has a parclo interchange with US 431 (21st Avenue, South Hillsboro Pike) some distance beyond.

I-440 then turns directly east and reaches I-65 south of downtown Nashville about two miles (3.2 km) later in the top level of a symmetrical four-level "Spaghetti Junction" stack interchange, which includes four flyover ramps.

Briefly entering the city of Berry Hill, the Interstate turns east-northeast and meets US 31A/US 41A (Nolensville Pike) about 1.5 miles (2.4 km) later at a final parclo interchange where it also passes under another CSX line.

Many residents of the areas near I-440 wanted TDOT to choose an alternative, such as constructing the route further to the south, widening existing surface streets, or adding more public transportation.

[12] Initially, I-440 was going to be at-grade, but TDOT engineers chose to build it below the surface of the ground to reduce noise and vehicle emissions pollution after citizens in large cities living near Interstates had complained of disturbances caused by highway traffic.

This included separating the lanes by a narrow grassy median, which unintentionally made the route susceptible to crossover crashes, and curbed inner edges.

[4] A proposed interchange at Granny White Pike, which TDOT had acquired the right-of-way for, was abandoned in an effort to prevent the disruption of traffic patterns on nearby surface streets.

[9][14] The discovery of hairline cracks in multiple overpasses and ramps in the spring of 1985, which were repaired with epoxy cement, delayed the opening of I-440 by approximately eight months.

[4] By 1999, the average annual daily traffic had surpassed 100,000 vehicles in some locations,[5] and the entire route had begun to experience severe congestion every day during rush hour.

[13] Between June and November 2013, TDOT spent $9.7 million to repair the concrete on I-440 eastbound between I-65 and I-24, which also included adding an additional lane through the interchange with US 31A/US 41A.

[13] After the Tennessee General Assembly passed the IMPROVE Act in 2017, which increased the state's fuel taxes and vehicle registration fees with the intent of funding a backlog of 962 needed transportation projects, TDOT announced that an upgrade of I-440 was a top priority.

[34][35] On February 21, 2021, I-440 was designated as the Debra K. Johnson Memorial Parkway in honor of a Tennessee Department of Corrections (TDOC) officer killed in the line of duty in 2019.