Lee-Smith’s artistic talent was nurtured by both his mother and grandmother. The Karamu House, the oldest African American theater, gave Lee-Smith a scholarship to attend the Cleveland Institute of Art (then the Cleveland School of Art). He graduated with an honors degree in 1938. He would later earn his Bachelor of Science in art education in 1953 from Wayne State University in Detroit. This fortified his love of teaching.

In 1943, Lee-Smith was awarded the Purchase Prize from Clark Atlanta University’s annual exhibition of African American artists. He was then included in the influential text Modern Negro Art, written by James A. Porter. Between 1943 and 1945, he served in the US Navy and was stationed near Chicago as an official “morale painter” tasked with making artworks that centered patriotic and historical themes. In Chicago, he encountered other Black artists, such as Charles White and Charles Sebree, who he met at Southside Community Arts Center where his first solo exhibition was mounted in 1945. At the end of the war, in 1945, he returned to Detroit, and to his artistic pursuits.

He was the second African American artist to be elected as a full member of the National Academy of Design, in 1967. The first was painter Henry Ossawa Tanner, in 1927. In addition to his artistic achievements, Lee-Smith dedicated himself to teaching and mentoring aspiring artists. He has held teaching positions at art institutions and organizations such as the Art Students League, Claflin College, Southside Community Arts Center, and Vermont Academy.

The Studio Museum in Harlem presented Lee-Smith’s works in numerous group exhibitions including The Fine Art of Collecting (1978); Impressions/Expressions (1979); and Their Own Harlems (2017). The Studio Museum first acquired work by Lee-Smith in 1997.