At this interchange, I-10 breaks off to the northeast and Business U.S. 90 begins. The expressway continues southeast along the upriver side of the CBD as an elevated highway that leads to the Crescent City Connection. This section was completed by 1958 opening of the Crescent City Connection.

The Business District U.S. 90 portion of the expressway was expanded in the mid 1980s to accommodate the second span of the Crescent City Connection which opened in 1988. This stretch of the expressway and the stack interchange of I-10 and U.S. 90 received further reconstruction in the early 1990s, including two reversible HOV (High Occupacy Vehicle) lanes that stretch from the intersection of Earhart Boulevard and Magnolia Street (underneath the Pontchartrain Expressway) across the Crescent City Connection to the Westbank Expressway.

Reconstruction of the northern end of the expressway in the I-610 Split vicinity was undertaken in the late 1990s. Also in the late 1990s, further work was done on the expressway as three ramps were constructed, one connecting East Business U.S. 90 to East I-10 and the others connecting West I-10 to West Business U.S. 90 and westbound Claiborne Avenue (West US 90).

The Norfolk Southern Railway has an overpass crossing near the Metairie Cemetery between the City Park Avenue and West End Boulevard/Florida Avenue exits. Here the expressway dips down to 12 feet below sea level to allow for the rail line to pass overhead. This area once experienced flooding on a regular basis in heavy thunderstorms and tropical systems. The problem was so common, a depth meter was painted on the overpass support columns to warn drivers of the water's depth. A new pumping station was completed adjacent to the expressway in 2004 to keep this area dry and allow the interstate to remain open in the event of an evacuation.

In the aftermath of Hurricane Katrina, this pumping station was overwhelmed and the railroad underpass and the entire I-610/West End Boulevard interchange was extensively flooded. In fact, the 17th Street Canal breach is about one mile north of this area. This flooding cut Orleans Parish off from most areas to the west, making the Crescent City Connection one of the few clear routes into the eastbank of Orleans Parish. Areas under the elevated portions of the expressway in the CBD area saw flooding in the vicinity of the Superdome but for the most part remained dry and undamaged. Some evacuaees trapped in the city for days after Katrina attempted to use the expressway and the Crescent City Connection to walk to dry ground on the West Bank.  Source: http://en.wikipedia.org/wiki/Pontchartrain_Expressway

All that remains of the New Basin Canal, which was used for much of the route of the Pontchartrain Expressway, is a short stretch at the lake between the Southern Yacht Club and the New Canal Lighthouse which runs south to Lake Marina Drive (viewed on the left).

St. John the Baptist parochial school at the corner of Dryades and Calliope Streets was demolished to make way for the elevated Pontchartrain Expressway.