In 1933 he landed his first job as a freelance journalist and from there his career took off. He was able to capture moments during the Spanish Civil War as well as during unrest in Czechoslovakia. In 1939 he took photographs of Loyalist Spanish refugees who journeyed to Mexico. When WWII began, Seymour was in New York but enlisted in the army in 1940 where he worked as a photo interpreter in Europe. In 1942 his parents were killed by Nazis, which lead him to help UNICEF document the plight of refugees, especially children.
Even though he was well known for his war photographs of orphans, he later got into photographing celebrities. While covering the 1956 Suez War, Seymour and fellow photographer Jean Roy were killed by machine-gun fire.