Between 1927–1934 Orozco lived in the USA. Even after the fall of the stock market in 1929, his works were still in demand. From March to June 1930, at the invitation of the Pomona College Art Department, he painted what he noted was the "first fresco painted outside the country by a painter of the Contemporary Mexican School."The fresco, Prometheus (Prometeo del Pomona College), on the wall of a Pomona College dining hall, was direct and personal at a time when murals were expected to be decorous and decorative, and has been called the first "modern" fresco in the United States.[8] Later that year, he painted murals at the New School for Social Research, New York City, now known as the New School University. One of his most famous murals is The Epic of American Civilization at Dartmouth College, New Hampshire, USA. It was painted between 1932 and 1934 and covers almost 300 m² (3200 square feet) in 24 panels. Its parts include: "Migrations", "Human Sacrifices", "The Appearance of Quetzalcoatl", "Corn Culture", "Anglo-America", "Hispano-America", "Science" and "Modern Migration of the Spirit" (another version of "Christ Destroys His Cross").
After returning to Mexico in 1935, Orozco painted in Guadalajara, Jalisco, the mural "The People and Its Leaders" in the Government Palace, and the frescos for the Hospicio Cabañas, which are considered his masterpiece. In 1940 he painted at the Gabino Ortiz Library in Jiquilpan, Michoacán. Between 1942–1944 Orozco painted for the Hospital de Jesús in Mexico City. Orozco's 1948 "Juárez Reborn" huge portrait-mural was one of his last works.

In 1947, Orozco illustrated the book The Pearl, by John Steinbeck.

Orozco died in 1949 in Mexico City.

Our Art collection Cantú Y de Teresa includes historical documents, books and photographs that describe one of the most important episodes in the history of art