After graduating from the Colorado Institute of Art in 1980, Mary Mackey began working as a freelance fashion photographer and photojournalist. Mackey then lived in Europe for a few years where she worked as a photography instructor and helped found an outdoor art gallery in Berlin, Germany. She returned to the United States and in the late 1980s began to explore printmaking and painting. Her earliest images were abstract; recognizable forms developed later.

In 1991 Mackey opened the Mackey Gallery in Denver, Colorado. Devoted to showing the works of thirty artists from the United States and elsewhere, the gallery quickly became known as one of Denver's best. However, when it became a full-time labor for Mackey she scaled it back to a framing business so that she could concentrate on her own art. Today Mackey is an active artist again.

Mackey's work has been shown in numerous exhibits, including those at the Charles Kristen Gallery in Denver and the Karan Ruhlen Gallery in Sante Fe, New Mexico. Her art is found in a number of collections, including the Boulder Museum of Contemporary Art in Colorado, Global Pacific in Denver and the Hotel Nikko Fukuoka in Japan.