Lionel Samson Reiss was born in Jaroslau, Austria on January 29, 1894. His family emigrated to America, arriving on June 20, 1900 at which point his middle name was changed to Samuel. Reiss grew up on Manhattan's Lower East Side. As immigrants to the United States, Reiss’ parents joined the ranks of other Eastern European Jews who were fleeing their native countries at the start of the 20th century. He married Frances Grossel on December 4, 1935.

Reiss became known for his portraits of Jewish people and landmarks in Jewish history, which he made during his trip to Europe, Africa, and the Middle East in the early 1920s. Being American and Jewish himself, Reiss became fascinated with Jewish life in the Old World. In 1919 Reiss temporarily left the United States to travel to the aforementioned regions, and recorded the everyday life that he encountered in the ghettos. Self taught as an artist this trip resulted in exhibitions in major American cities.

At the dawn of the Holocaust in 1938, Reiss, who had long returned to the United States, published his book My Models Were Jews, in which he illustratively argued that there is no such thing as a "Jewish ethnicity", but the Jewish people are rather a cultural group, whereby there is significant diversity within Jewish communities and between different communities in different geographical regions. Reiss was therefore presenting an argument against what he considered to be a common misconception that existed about the Jews. Later works included a 1954 book, New Lights and Old Shadows, which dealt with "the new lights" of a reborn Israel and the "old shadows" of an almost eradicated European Jewish culture. In his last book, A World of Twilight, published in 1972, with text by Isaac Bashevis Singer, Reiss presented a portrait of the Jewish communities in Eastern Europe before the Holocaust.

Reiss worked as a commercial artist for newspapers, publishers, and a motion picture company. in the early 1920s he became an art director for Paramount Studios and is credited with being the creator of the Leo the Lion logo of Metro-Goldwyn-Meyer Studios.

Lionel Samson Reiss died on April 16, 1988 in New York.