She married Charles Kirtley Brown in 1939, and they lived in Auburn until they inherited her father's farm in Perry County. She published a few short stories in literary magazines, but she put her writing aside until her son, Kirtley Ward Brown, was grown and her husband's death in 1970.

After she resumed her writing, she published some stories in short-story collections and periodicals. In 1978 McCall's magazine published her story "Amaryllis", about a flower a retired judge received as a gift and his efforts to have others see it bloom.

Her first collection of short stories, Tongues of Flame, was published in 1986, and received much acclaim. Following the success of that book, she gained increasing prominence in southern and national literary circles. In 2002, the University of Alabama Press published her second collection of short stories, It Wasn't All Dancing. In 2009, the University of Alabama Press also published her memoir, Fanning the Spark.

Using the setting and characters of her Black Belt home, she wrote about race, class, religion, family and generational conflicts in a way that revealed the universal traits of these subjects. In the 2001 documentary film Coat of Many Colors, she discussed conflicts within southern culture, the subtleties of southern race relations and the slow progress of change in the civil rights era.

Brown's stories of black and white characters was so beautifully sensitive and nuanced, she was selected to be one of 40 prominent American and Soviet writers to attend a joint writer's conference in Russia to help thaw Cold War relations between the two nations.

Brown won many awards, including: Pen/Hemingway Award (for best book of fiction by an American author) 1987; Lillian Smith Award from the Southern Regional Council; Harper Lee Award for Alabama's Distinguished Writer 2002; Hillsdale Fiction Prize from the Fellowship of Southern Writers 2003.

She was inducted into the Alabama Black Belt Hall of Fame in 2012 and the Alabama Writers Hall of Fame in 2016.

Historian Wayne Flynt said that Brown was "probably the most famous Alabamian you never heard of". Southern journalist John S. Sledge called Brown "our genius, our Chekov".