After graduating from Harvard in 1926, Cullen worked as an editor for Opportunity magazine. In 1928, he married Yolande Du Bois, the daughter of W.E.B. Du Bois. They then went to France, where Cullen would study at the Guggenheim Fellowship. After the release of his first book, The Black Christ and Other Poems, his reputation as a poet began to decline. Among his other works are The Medea and Some Poems and The Ballad of the Brown Girl.
He also taught in New York City schools until his death in 1934. During this period, Cullen was struck by the use of racial themes in his verse, and he was criticized for using classical forms instead of using the rhythms and idioms of his African American heritage. He was also heavily influenced by John Keats. As well as writing books, Cullen promoted other black writers. However, in the 1930's his reputation began to quake. He published One Way to Heaven his only novel being a social comedy featuring low class blacks and New Yorkers.
Cullen married Yolande DuBois in April 1928. She was the surviving child of W.E.B. Du Bois and his first wife Nina Gomer Du Bois, whose son had died as an infant. The two young people were said to have been introduced by Cullen’s close friend Harold Jackman. They met in the summer of 1923 when both were in college: she was at Fisk University, and he was at NYU. Cullen’s parents owned a summer home in Pleasantville, New Jersey near the Jersey Shore, and Yolande and her family were likely also vacationing in the area when they first met. The marriage was the social event of the decade, but the marriage did not fare well, and he divorced in 1930. It is rumored that Cullen was a homosexual, and his relationship with Harold Jackman was a significant factor in the divorce. Jackman was a teacher whom Van Vechten had used as a model in his novel Nigger Heaven.
Cullen developed an image that incorporated both black and white cultures as a result of his blended identity. He was a firm believer in the power of poetry to transcend race and to bring people of different races closer together. Despite the fact that race was a constant element in his writing, Cullen desired to be regarded as a poet who was not defined solely by race. Countee Cullen's Eurocentric literary style arose from his exposure to Graeco-Roman Classics and English Literature while attending elite universities such as New York University and Harvard. Cullen uses Greek methods to analyze race and identity in his collection of poetry To the Three for Whom the Book and writes about Medusa.
Countee Cullen spent his final years primarily creating plays. He assisted in the adaptation of Arna Bontemps' novel God Sends Sunday into the musical St. Louis Woman. He also wrote an English translation of the Greek tragedy Medea. Due to excessive blood pressure, Countee Cullen died on January 9, 1946. He was laid to rest in The Bronx's Woodland Cemetery.