She is the creator and director of Denene Millner Books, an imprint of Simon & Schuster, and MyBrownBaby.com, a critically acclaimed blog that examines the intersection of parenting and race.

[6] Millner has written and collaborated on over 30 books of fiction, non-fiction, and youth literature including co-authoring six New York Times best sellers: Act Like a Lady, Think Like A Man (in paperback and hardcover),[7] Straight Talk, No Chaser (both with comedian Steve Harvey),[8] I Am Charlie Wilson with R&B performer Charlie Wilson,[9] Around the Way Girl with actress Taraji P. Henson,[10] and Believing in Magic with Cookie Johnson.

[13] Millner co-wrote three novels and three books of non-fiction with her former husband Nick Chiles,[14] including Love Don't Live Here Anymore and What Brothers Think, What Sistahs Know, both Essence best sellers.

[16] In 2019, Millner began hosting Speakeasy with Denene, a Georgia Public Broadcasting podcast that uses "art, culture, and entertainment to explore the beauty and humanity of blackness,"[17] and served as executive producer on the made-for-TV movie Angrily Ever After.

Millner describes her imprint as "a love letter to children of color who deserve to see their beauty and humanity in the most remarkable form of entertainment on the planet: books.