From the south, I-55 begins at an interchange with I-10 (exit 210) at the northern edge of LaPlace, an unincorporated community located about 20 miles (32 km) west of New Orleans.

The community situated along the pass is called Manchac and features a number of boat houses and fishing camps flanking the highway.

The surroundings having transitioned from swampland to pine forest, I-55 skirts the western edge of Ponchatoula, which is served by a cloverleaf interchange with Louisiana Highway 22 (LA 22).

[11] During his lengthy term in the US House of Representatives, Hammond native James H. Morrison (1908–2000) was responsible for securing 40 percent of Louisiana's Interstate Highway System and was instrumental in getting I-12 routed through the city.

[14] Construction of the system was finally authorized by the Federal Aid Highway Act of 1956, which was signed into law by President Dwight D. Eisenhower on June 29 of that year.

[15] The route was officially designated as I-55 on August 14, 1957,[16] and was part of the 602 miles (969 km) of Interstate Highway initially allocated to the state of Louisiana.

[22][23][b] Spanning 5.4 miles (8.7 km), the bypass was designed to connect seamlessly with US 51 at either end, facilitating the flow of traffic around the westside of both downtown areas and eliminating four right-angle turns.

[23][24] The construction of I-55 running northward from Hammond to the Mississippi state line, a distance of 37.4 miles (60.2 km), was completely underway by the autumn of 1964.

When construction of the Interstate Highway System was authorized in 1956, the swamp section of US 51 was in the process of being entirely rebuilt on an improved embankment adjacent to the original 1927 roadbed, which was narrow and suffering from subsidence.

[34] In November 1971, the Louisiana Department of Highways announced that the plans for I-55 had changed to consist of twin two-lane viaducts from the Manchac area southward with the existing ground-level US 51 serving as a frontage road alongside the northbound span.

[35] The highway department and local residents lobbied to have the entire route elevated on the basis that a ground-level roadway north of Manchac would negatively impact the swamp's ecosystem and also be unstable in the long term.

In October 1974, however, the agency relented after overwhelming local opposition and an environmental impact survey were presented during a series of public hearings.

A canal was dredged through the swamp along the entire right-of-way, allowing prestressed concrete roadway segments to be floated in by barge from the contractor's plant across Lake Pontchartrain.

Several vehicles plunged off the bridge, but the only fatality was ironically an employee of the construction firm building the I-55 spans who happened to be traveling on the highway at that time.

[42][43] The remainder of the distance north from Ruddock to Ponchatoula, including the new Pass Manchac bridge, was completed and opened to traffic following its dedication by Governor Edwin Edwards on May 25, 1979.

[50] Another project before the turn of the century was the addition of a diamond interchange at LA 3234 (Wardline Road) near Hammond, improving access to Southeastern Louisiana University.

[56][57] Though shortening the life expectancy of the highway, this method had the benefit of being quicker and more cost-effective than replacing the concrete panels and would require less maintenance over time.

Additionally, since I-55 is a designated hurricane evacuation route, the highway could be fully opened to traffic during construction within 48 hours' notice if needed.