He matriculated to Hampton Institute (now Hampton University) where a chance enrollment in a course with Viktor Lowenfeld which led to a life-long bond with the instructor. His friendships with Catlett, White, artist Hale Woodruff, and writer-philosopher Alain Locke (whom he met at Hampton) endured as well. When Lowenfield transferred to Pennsylvania State University, however, Biggers soon followed his mentor where he obtained both a masters and doctoral degree from the University.

His interaction with Lowenfield, artists, and intellectuals of his time influences on Biggers’ style. Lowenfeld, encouraged Biggers to explore the “the meaning of Negro Art Expression.” That he did so is evident in the adeptness at which Biggers’ evokes emotional responses to his images such as his "Dying Soldier." Images such as his "Going to Church," however, pay homage to his southern roots and Christian upbringing. They also provide some insight into the artist’s technical prowess as a skilled and tactical draftsman. Biggers works on paper appear to “be sculpted” out of dramatic lighting and strategically placed cross-hatching marks.

“As an artist, Biggers is best known for his murals, although he was also well respected for his drawings, prints, and sculpture. His influences, including African art and Southern African-American culture, are clearly visible in his art. In the 1940s Biggers portrayed social realism by painting what he saw as a young African American man. His transformed during the 1950s, particularly after his trip to Africa, when he began painting pictures that portrayed traditional African culture. As Biggers aged, his murals became more abstract and symbolic. His works often contained shotgun houses, churches, or railroads, which were symbolic of Black culture, spiritual rebirth, and travel.”

In the 1950’s, Biggers who visited Africa, began incorporating other African and diasporic inspired motifs and themes in his work. Along with the African inspired motifs, Biggers incorporated geometric abstract form and symbols, and emphasized Social Realism. Biggers continued to paint these symbolic works well into his retirement. These stylistic shifts are evident in his works from this period.

In 1995, The Art of John Biggers: View from the Upper Room, the Museum of Fine Arts, Houston, honored his work in a one-man travelling exhibition. The tribute was particularly significant. Because of the museum in 1950, had not allowed Biggers to attend a reception in honor of his first prize-winning entry at the then-segregated institution.