New Orleans was founded officially in 1718 by the Bienville brothers. These were French Canadians and were actually teenagers who declared on this spot on the crescent of the river to be a perfect place to found the port.
The reason this spot was chosen, although some were pressing for a spot in Manchac to be the city since it was on higher ground, but Manchac is not on the Mississippi River. Manchac could be accessed through Lake Pontchartrain which lies north of the present New Orleans, and would have access directly through the lake through a pass known as the Rigolets and only a few miles out to the Gulf of Mexico. But that was far from the river.
So it made more sense to have the city on the river. The Mississippi became the superhighway for travel and trade directly into the heart of the United States. Almost immediately after its founding the streets of the city, now the French Quarter were laid out in a 6 x 13 block rectangle, with a Place d’arms facing the river today known as Jackson Square.
Some of the original street names of the Vieux Carre (old square), another name for the Quarter are still used today.