The cathedral is named for Saint Louis and was designated a basilica by Pope John Paul II in 1997.

Although workers began clearing ground for the building on May 1, 1907, dedication of the cathedral and its first Mass did not take place until October 18, 1914, when the superstructure was complete.

A ceremony was conducted on May 1, 1907, for the groundbreaking of the site, and a formal laying of the building's cornerstone took place on October 18, 1908.

On December 20, 1943, a Solemn Pontifical Mass of Requiem was offered for Butch O'Hare, US Navy fighter pilot and Medal of Honor winner.

The grounds of the cathedral also contain the distinctive circular Chancery Building, c. 1965, designed by the Peruvian-American modernist architect Wenceslaus Sarmiento.

[6] The narthex of the church depicts the life of King Louis IX of France, namesake of the city and church, the rear dome includes mosaics of significant archdiocesan events, while the main dome by Jan Henryk de Rosen depicts Biblical scenes from both the Old Testament and New Testament.

In 1999, a 14-foot high, welded stainless steel sculpture by Wiktor Szostalo was installed on the side lawn of the church.

The statue's base is of granite and is inscribed with quotations from the New Testament, Pope John Paul II, and Martin Luther King Jr.

The sculpture emphasizes a theme of harmony, peace, and racial justice, according to Auxiliary Bishop Edward Braxton, who suggested the project to Archbishop Justin Rigali.

[12] The statue was vandalized and destroyed by a 35-year-old man, who tampered with construction equipment being used for renovations on the cathedral on September 17, 2024.