Mark Rothko (Marcus Rothkowitz, Mark Rotkovich) was born in Dvinsk, Vitebsk Province, Russian Empire (now Daugavpils, Latvia). His father, Jacob Rothkowitz, was a pharmacist and an intellectual, who provided his children with a secular and political, rather than religious, upbringing. Unlike Jews in most cities of Czarist Russia, those in Dvinsk had been spared from violent outbreaks of anti-Semitic pogroms. However, in an environment where Jews were often blamed for many of the evils that befell Russia, Rothko’s early childhood was plagued with fear.

Despite Jacob Rothkowitz's modest income, the family was highly educated, and able to speak Russian, Yiddish and Hebrew. Following Jacob's return to Orthodox Judaism, he sent Marcus, his youngest son, to the cheder at age 5, where he studied the Talmud although his elder siblings had been educated in the public school system.

Fearing that his sons were about to be drafted into the Czarist army, Jacob Rothkowitz emigrated from Russia to the United States, following the path of many other Jews who left Daugavpils in the wake of Cossack purges. These émigrés included two of Jacob's brothers, who managed to establish themselves as clothing manufacturers in Portland, Oregon, a common profession among Eastern European immigrants. Marcus remained in Russia with his mother and elder sister Sonia. They joined Jacob and the elder brothers later, arriving at Ellis Island in the winter of 1913 after 12 days at sea. Jacob's death a few months later left the family without economic support. One of Marcus’ great aunts did unskilled labor, Sonia operated a cash register, while Marcus worked in one of his uncle’s warehouses, selling newspapers to employees.

Marcus started school in the United States in 1913, quickly accelerating from third to fifth grade, and completed the secondary level with honors at Lincoln High School in Portland, in June 1921 at the age of 17. He learned his fourth language, English, and became an active member of the Jewish community center, where he proved adept at political discussions. Like his father, Rothko was passionate about such issues as workers’ rights and women's right to contraception.

He received a scholarship to Yale based on academic performance, but it has been suggested that Yale only made this offer in order to lure Rothko’s friend, Aaron Director, with a similar proposal. After one year, the scholarship ran out and Rothko took menial jobs to support his studies.

Rothko found the "WASP" Yale community to be elitist and racist. He and Aaron Director started a satirical magazine, The Yale Saturday Evening Pest, which lampooned the school’s stuffy, bourgeois attitude. Following his second year, Rothko dropped out, and did not return until he was awarded an honorary degree 46 years later.

In the autumn of 1923, Rothko found work in New York's garment district and took up residence on the Upper West Side. While visiting a friend at the Art Students League of New York, he saw students sketching a model. According to Rothko, this was the beginning of his life as an artist. Even his self-described "beginning" at the Art Students League of New York was not whole-hearted commitment; two months after he returned to Portland to visit his family, he joined a theater group run by Clark Gable’s wife, Josephine Dillon. Whatever his dramatic ability may have been, he looked nothing like the successful actors of the day, and professional acting seemed an improbable career.

Returning to New York, Rothko briefly enrolled in the New School of Design, where one of his instructors was the artist Arshile Gorky. This was probably his first encounter with a member of the "avant-garde". That autumn, he took courses at the Art Students League of New York taught by still-life artist Max Weber, a fellow Russian Jew. It was due to Weber that Rothko began to see art as a tool of emotional and religious expression, and Rothko’s paintings from this era reveal a Weberian influence.

Rothko’s move to New York established him in a fertile artistic atmosphere. Modernist painters had shows in the New York galleries, and the city’s museums were an invaluable resource to foster a budding artist’s knowledge, experience and skills. Among those early influences were the works of the German Expressionists, the surrealist work of Paul Klee, and the paintings of Georges Rouault. In 1928, Rothko exhibited works with a group of other young artists at the appropriately named Opportunity Gallery. His paintings included dark, moody, expressionist interiors, as well as urban scenes, and were generally well accepted among critics and peers. Despite modest success, Rothko still needed to supplement his income, and in 1929 he began giving classes in painting and clay sculpture at the Center Academy, where he remained as teacher until 1952. During this time, he met Adolph Gottlieb, who, along with Barnett Newman, Joseph Solman, Louis Schanker, and John Graham, was part of a group of young artists surrounding the painter Milton Avery, fifteen years Rothko’s senior. Avery’s stylized, natural scenes, utilizing a rich knowledge of form and color, would be a tremendous influence on Rothko. Soon Rothko's paintings took on Averian subject matter and color, as in Bathers, or Beach Scene of 1933/34.

Rothko, Gottlieb, Newman, Solman, Graham, and their mentor, Avery, spent considerable time together, vacationing at Lake George and Gloucester, Massachusetts, spending their days painting and their evenings discussing art. During a 1932 visit to Lake George, Rothko met Edith Sachar, a jewelry designer, whom he married on November 12. The following summer, Rothko’s first one-man show was held at the Portland Art Museum, consisting mostly of drawings and aquarelles, as well as the works of Rothko’s pre-adolescent students from the Center Academy. His family was unable to understand Rothko’s decision to be an artist, especially considering the dire economic situation of the Depression. Having suffered serious financial setbacks, the Rothkowitzes were mystified by Rothko’s seeming indifference to financial necessity; they felt he was doing his mother a disservice by not finding a more lucrative and realistic career.