Charles Henry "Spinky" Alston was born in Charlotte, North Carolina on November 28th, 1907. Early artistic influences included his father's, Reverend Primus Priss, illustrated courtship letters to Charles' mother, Anna Miller. Alston also recalled his older brother's drawings of cars and trying to copy them. After the death of his father, Alston's mother married Henry Pierce Bearden (Romare Bearden's uncle) in 1913 and the family moved to New York City.

At DeWitt Clinton High School in New York, Alston served as art editor of the school's literary magazine. Alston majored in fine arts and history at Columbia University, graduating in 1929. He became active in the Harlem community and accepted a position as director of Utopia House, a boy's camp, where he started an art program. He returned to Columbia and recieved a Masters degree in art education from Columbia's Teachers College. While still a student, he illustrated album covers for jazz musician Duke Ellington and book covers for poet Langston Hughes.

Alston played a major role in the Harlem Renaissance Movement of the period. During the Great Depression, he and sculptor Henry Bannarn directed the Harlem Art Workshop which was funded by the Works Progress Administration Federal Art Project. There he taught and mentored African-American painter Jacob Lawrence, as well as Romare Bearden, among others.

Alston painted murals throughout Harlem, including depression-era murals as part of the WPA. One of his best-known murals was created by Alston and other Harlem artists for the Harlem Hospital Center. Despite some opposition to the murals because of the numbers of African-Americans prominent in the design sketches, the project moved forward with the financial support of Louis T. Wright, the first African-American physician to serve on the hospital's staff, and community support. Artists who worked on the murals included Georgette Seabrooke, Vertis Hayes, Alfred Crimi, Beauford Delaney, and photographer Morgan Smith.

Recognizing the lack of African-American artists associated with the WPA, Alston also helped form the Harlem Artists Guild which pressured the federal program to be more inclusive.

In the 1950s, Alston embarked on a series of portraits of African-American figures. He also taught at the Art Students League and later with the City College of New York (CUNY). Along with his wife, Myra Logan - a surgeon at Harlem Hospital, Alston lived in Harlem and remained an active member of the community until the very end of his life. Charles Alston died in 1977.