In May 1946, commercial air service began at Moisant Field, named for aviation pioneer John Bevins Moisant. By January 1947, the airport was considered to be one of the largest commercial airports in the nation encompassing 1360 acres of land that included three 5,000 foot runways and one 7,000 foot runway. In addition, it was the first airport to install an Instrument Landing System. In 1959, a new terminal and two new concourses were dedicated. The official name of the airport was changed in 1960 from Moisant Field to New Orleans International Airport.

In August 2005, Hurricane Katrina struck the Louisiana-Mississippi Gulf coastline resulting in massive destruction and loss of life. The airport played a vital role in evacuating over 30,000 evacuees to safety. For three days, Armstrong International Airport was the busiest airport in the world. Commercial flights resumed service in September 2005, while the airport continued to play a variety of support roles in the rescue and recovery effort of the region.

On November 6, 2019, the new world-class terminal at Louis Armstrong New Orleans International Airport officially opened to the public.

The three letter identifier for Louis Armstrong New Orleans International Airport is MSY. It stands for Moisant Stock Yards.