Samella Sanders Lewis received numerous honors over her lifetime. One 2011 tribute described her as an “iconic figure in American art” and sought to summarize her myriad contributions as an “educator, curator, museum founder, art historian, arts administrator and more. Her long, distinguished career includes four degrees, five films, nine books, and a substantial body of artworks which have received great critical regard.” In all these pursuits, Lewis was a peerless advocate for African American engagement with the arts. Accomplished in a variety of media, Lewis was best known as a printmaker. She often depicted human "figures that express ideas, feelings or social conflicts, not personalities.” Migrants, “inspired by a miserable group of Florida bean pickers seated in the back of a truck," is representative of these anonymous portrayals turned political commentary.

A childhood spent in segregated New Orleans exposed Lewis to racial prejudice; as she matured, art offered a powerful vehicle to express her response to injustice. She was influenced early on by comic books, an affinity borne out in the graphic art she later created. In 1941, she enrolled at nearby Dillard University, where she met her mentor and lifelong friend Elizabeth Catlett. Catlett recognized Lewis’s remarkable potential and advised her to transfer to Hampton Institute. Lewis graduated from Hampton—where John Biggers was among her classmates—in 1945. At the recommendation of her instructor Viktor Lowenfeld, she immediately joined the school’s art faculty and taught for two years. Lowenfeld encouraged her to attend graduate school, suggesting Ohio State University. Lewis initially planned to pursue a printmaking degree but took so many courses in art history that she majored in “studio art history,” effectively combining two master’s degrees. She received her PhD from OSU in 1951, becoming the first female African American to earn a doctorate in art history. While completing her dissertation, Lewis taught at Morgan College (now Morgan State University) in Baltimore. She moved to Tallahassee in 1953 to establish, and later lead, the art department at Florida Agricultural and Mechanical University, which quickly became one of the largest available at an historically black college or university. That same year, she organized the first professional conference for African American artists, the National Conference of Artists. 

As a graduate student, Lewis developed an interest in Asian art, which she continued to foster when she moved to the State University of New York in Plattsburgh in 1958. A Fulbright fellowship for study in Taiwan afforded her the chance to expand her research in the field, followed by postdoctoral classes at the University of Southern California and New York University. Although she liked Plattsburgh’s progressive curriculum, Lewis relocated to Los Angeles, so her children could experience a more multicultural population.

In 1968, Lewis became the education coordinator at the Los Angeles County Museum of Art, a position she had hoped to use to increase exhibition opportunities for African American artists. Frustrated by the lack of black representation in larger museums' collections and staffs, Lewis resigned. She would go on to establish three independent art galleries and, in 1976, founded the Museum of African American Art in Los Angeles, where she worked as senior curator until 1986. Soon after she left LACMA, Lewis began teaching at Scripps College in Claremont, California (1969–1984), and, in another first, became the college’s first tenured African American professor. When she and fellow artist-scholar Ruth Waddy sought to publish their landmark two-volume guide on African American artists, Black Artists on Art (1969 and 1971), Lewis co-founded Contemporary Crafts Gallery, the first African American–owned art publishing house. She launched the noted academic journal, International Review of African American Art, in 1976. Her documentary interviews with prominent African American artists, such as Catlett and Richmond Barthé, were eventually published in the seminal text Art: African American (1978). During this same period, she made several short films celebrating the careers of African American artists. 

In recognition of her contribution to the arts and specifically to the field of African American art history, Samella Lewis received the UNICEF Award for the Visual Arts in 1995. She was also a distinguished scholar at the Getty Center for the History of Art and the Humanities in Los Angeles from 1996 to 1997. Her work can be found at national art museums such as the Museum of Modern Art, the Metropolitan Museum of Art, and the Hampton University Museum.