The Saenger Amusement Company purchased this lot on Canal Street in 1921 for $250,000 with plans to erect a lavish million-dollar theater.  The Saenger Theater opened its doors on February 5, 1927.  The venue began as a silent movie house, with a ticket box office and main entrance at 1111 Canal Street. 
The Saenger Theatre, while part of the larger Saenger Amusement Company theater chain, was the company's flagship venue. The Saenger was exceptionally ornate, including life-size and smaller statues, crystal lighting fixtures, oil paintings, and fine crystal.  The Saenger was deemed “lavish and beautiful,” with two different arcades that contained all the amenities, men’s lounges, women’s powder rooms, smoking rooms, a mezzanine, and a seating capacity of 4000 persons. 
A staple of the early days of the Saenger Theater was the between-show recital on the Mammoth Theater Organ. A Times-Picayune article in 1960 noted that the Organ initially accompanied silent movie pictures with mood cues such as “mysterioso,” “hurry,” “love scene,” and “gallop.” Bob Mack, a theater organist, noted how the organ could “imitate with uncanny accuracy the songs of birds, the roar of jungle beasts, the lowing of cows, the barking of dogs, the mewing of cats and the howls of wolves." 
When the Saenger first opened its doors, it competed with the Keith-Orpheum and Loew circuits to attract vaudeville acts. As a result, The Saenger struggled to offer a comparable quality and variety of entertainment to their audiences.  Just two years after its opening, Saenger Theater was sold to the Paramount-Publix chain for more than $10 million.  Aware of Saenger Theater's inability to draw first-class entertainment, the new management moved quickly to install a sound system and capitalize on the growing motion picture enterprise.  By June 1933, the Saenger had discontinued vaudeville entirely and offered only first-rate sound films distributed by Paramount Pictures. 
In February 1964, the Saenger made plans to convert the real estate into two movie auditoriums, or what’s known as a piggyback theater. The upstairs portion of the theater would seat 900 customers, the downstairs 1,900. The manager at the time, Walter Guarino, expected to convert the lesser area for road-show attractions, extended-run films, or as he put it, “whatever the product is.”  The addition of another screen was an effort to catch up with the times. By the 1960s, the Saenger's single auditorium was a classic version of the movie house, already vintage in the eyes of movie houses with multiple auditoriums and a selection of movies. The renovation was viewed with disdain by many locals. 
Ultimately, however, there was an attempt made in 1960 to preserve the historic Saenger Theater. Manager Walter Guarino issued a public request in the New Orleans States-Item, soliciting the help of locals to piece together the history of the Saenger Theater. Guarino requested photographs, programs, brochures, and newspaper clippings about the early days of the Saenger. The article noted that Guarino wanted to revamp the theater to its original state.