It was there that Pichel achieved considerable acclaim as the title character in the landmark Pasadena Playhouse production of Eugene O'Neill's play Lazarus Laughed in 1927.

Pichel worked steadily as a character actor throughout the 1930s, including the early version of the Theodore Dreiser novel, An American Tragedy (1931), Madame Butterfly (1932), in a low budget version of Oliver Twist (1933) as Fagin, in Cleopatra (1934), alongside Leslie Howard in Michael Curtiz's British Agent (1934), as the servant Sandor in Dracula’s Daughter (1936), in the Bette Davis film Jezebel (1938), as the proprietor of a seedy roadhouse in the once scandalous The Story of Temple Drake (1933) and as a Mexican general in Juarez (1939).

The Man I Married (1940), for example, starring Joan Bennett, Francis Lederer, and Otto Kruger, centers on an American wife slowly discovering her German husband is a Nazi, and incorporated 1938 newsreel footage of the rise of Nazism.

Hudson’s Bay (1941) was a highly pro-British, much-fictionalized historical adventure of the British founding of Canada with Paul Muni and Gene Tierney.

With a screenplay by future blacklisted writer, Nunnally Johnson, this was named as one of the top ten films of the year by the National Board of Review.

The film showed Ladd finding love in occupied France under the auspices of the nascent O.S.S., which was the precursor to the Central Intelligence Agency.

Tomorrow Is Forever, (1946) starred Orson Welles as an American soldier who is presumed killed in WW1 only to return to America and Claudette Colbert as his wife who remarries; Natalie Wood, in her first credited role, plays an Austrian child with a German accent.

Made about the same time was The Miracle of the Bells (also 1948), a big budget film which failed at the box office about an impoverished coal town with Frank Sinatra miscast as a priest.

The low-budget, black-and-white Quicksand (1950) featured one of Mickey Rooney's finest performances as a desperate good kid going bad, and emigre Peter Lorre as an unforgiving arcade operator.

Striking out in another nascent genre, Pichel pioneered scientific authenticity in an early Technicolor science fiction film Destination Moon (1950), produced by George Pal.

"[12] Pichel chose as collaborators Robert A. Heinlein, who did uncredited work on the script, and astronomical illustrator Chesley Bonestell,[13] who contributed the painted lunar backdrops.

Shot on location in Wiesbaden, Germany, Martin Luther was nominated for Oscars for both its black-and-white cinematography by Joseph C. Brun, and its art direction and set design recreating the early 1500s by Fritz Maurischat and Paul Markwitz.

In 1947, Pichel was one of 19 members of the Hollywood community who were subpoenaed by the House Un-American Activities Committee during the United States' second Red Scare.

[15] While Pichel was ultimately not called to testify,[16] he was blacklisted, forcing him eventually to leave the United States in order to direct his final pictures.