In 1914, Moreno began co-starring in a series of highly successful serials at Vitagraph opposite popular silent film actress Norma Talmadge.

By the early 1920s, Moreno joined film mogul Jesse Lasky's Famous Players and became one of the company's highly paid performers.

[citation needed] With the advent of sound films in the late 1920s and early 1930s, Moreno's career began to falter, in part because of his heavy Spanish accent.

On January 27, 1923, Moreno married American heiress Daisy Emma Canfield in Los Angeles, California.

In 1994, the Mexican magazine Somos published its list of "The 100 best movies of the cinema of Mexico" in its 100th edition and named the 1931 Moreno directed Santa its 67th choice.