Endsley was born in California and grew up in Phoenix, Arizona, and Houston, Texas, where she attended Spring Woods High School.

From 1997 to 2013, Endsley served as president and CEO of SA Technologies in Marietta, Georgia, a cognitive engineering firm specializing in the development of operator interfaces for advanced systems, including the next generation of systems for aviation, air traffic control, medical, power, oil & gas, and military operations.

This human-centered design approach has been found to be critical to successfully integrating people with advanced technologies and automation in a wide variety of domains.

She is Past-President of the Human Factors and Ergonomics Society where she is a fellow, was co-founder of the Cognitive Engineering and Decision Making Technical Group of HFES, and has previously served on its Executive Council.

Endsley received the Human Factors and Ergonomics Society Jack Kraft Innovator Award in 2003 for her work in situation awareness.