I-12 parallels the older US 190 corridor and traverses the north shore of Lake Pontchartrain in the southeastern portion of the state.

Apart from serving the various communities of the North Shore, I-12 acts as a long bypass of New Orleans and is heavily used as a shortcut for through traffic on I-10.

While I-10 curves to the south to pass through the city limits, I-12 takes a more direct alignment, reducing the distance between Baton Rouge and Slidell by about 22 miles (35 km).

While I-10 heads to the southeast toward the New Orleans metropolitan area, I-12 proceeds eastward toward the North Shore of Lake Pontchartrain.

[2][5][6] Shortly after crossing the Natalbany River into Tangipahoa Parish, I-12 intersects LA 1249, which leads to the communities of Baptist and Pumpkin Center.

I-12 enters into a cloverleaf interchange 3.2 miles (5.1 km) later with I-55 at the southeast corner of Hammond, the largest city in Tangipahoa Parish.

Just after crossing into St. Tammany Parish, I-12 curves to the southeast and begins to parallel the North Shore of Lake Pontchartrain.

This section of US 190 serves as St. Tammany Parish's busiest north–south thoroughfare, connecting Covington and surrounding points with the Lake Pontchartrain Causeway, a 24-mile-long (39 km) bridge leading to New Orleans.

[12][13] With major damage to the I-10 Twin Span Bridge across Lake Pontchartrain from Hurricane Katrina, I-12 was temporarily functioning as I-10 between Baton Rouge and Slidell.

The westbound span of I-10 reopened on January 6, 2006, with speed, weight and size restrictions, relieving I-12 of much of the congestion that was clogging it from the Lake Pontchartrain Causeway to the junction with I-10 and I-59.