Coleman graduated from Wilbert Tucker Woodson High School, Fairfax, Virginia, in 1978; in 1978–1979, she was an exchange student at Røyken upper secondary school in Norway with the AFS Intercultural Programs. She received a bachelor of science degree in chemistry from the Massachusetts Institute of Technology in 1983, and a doctorate in polymer science and engineering from the University of Massachusetts Amherst in 1991 as a member of the Air Force ROTC. She was advised by Professor Thomas J. McCarthy on her doctorate. She was a member of the intercollegiate crew and was a resident of Baker House.
After completing her regular education, Coleman joined the U.S. Air Force as a Second Lieutenant while continuing her graduate work for a PhD at the University of Massachusetts Amherst. In 1988 she entered active duty at Wright-Patterson Air Force Base as a research chemist. During her work she participated as a surface analysis consultant on the NASA Long Duration Exposure Facility experiment. In 1991, she received her doctorate in polymer science and engineering. She retired from the Air Force in November 2009.
Coleman was selected by NASA in 1992 to join the NASA Astronaut Corps. In 1995, she was a member of the STS-73 crew on the scientific mission USML-2 with experiments including biotechnology, combustion science, and the physics of fluids. During the flight, she reported to Houston Mission Control that she had spotted an unidentified flying object. She also trained for the mission STS-83 to be the backup for Donald A. Thomas; however, as he recovered on time, she did not fly that mission. STS-93 was Coleman's second space flight in 1999. She was mission specialist in charge of deploying the Chandra X-ray Observatory and its Inertial Upper Stage out of the shuttle's cargo bay.
Coleman served as Chief of Robotics for the Astronaut Office, to include robotic arm operations and training for all Space Shuttle and International Space Station missions. In October 2004, Coleman served as an aquanaut during the NEEMO 7 mission aboard the Aquarius underwater laboratory, living and working underwater for eleven days.
Coleman was assigned as a backup U.S. crew member for Expeditions 19, 20 and 21 and served as a backup crew member for Expeditions 24 and 25 as part of her training for Expedition 26.
Coleman launched on December 15, 2010 (December 16 Baikonur time), aboard Soyuz TMA-20 to join the Expedition 26 mission aboard the International Space Station. She retired from NASA on December 1, 2016.
STS-73 on Space Shuttle Columbia (October 20 to November 5, 1995) was the second United States Microgravity Laboratory mission. The mission focused on materials science, biotechnology, combustion science, the physics of fluids, and numerous scientific experiments housed in the pressurized Spacelab module. In completing her first space flight, Coleman orbited the Earth 256 times, traveled over 6 million miles, and logged a total of 15 days, 21 hours, 52 minutes and 21 seconds in space.
STS-93 on Columbia (July 22 to 27, 1999) was a five-day mission during which Coleman was the lead mission specialist for the deployment of the Chandra X-ray Observatory. Designed to conduct comprehensive studies of the universe, the telescope will enable scientists to study exotic phenomena such as exploding stars, quasars, and black holes. Mission duration was 118 hours and 50 minutes.
Soyuz TMA-20 / Expedition 26/27 (December 15, 2010, to May 23, 2011) was an extended duration mission to the International Space Station.
Coleman is married to glass artist Josh Simpson who lives in Massachusetts. They have one son. She is part of the band Bandella, which also includes fellow NASA astronaut Steven Robinson, Canadian astronaut Chris Hadfield, and Micki Pettit (astronaut Don Pettit's wife). Coleman is a flute player and has taken several flutes with her to the ISS, including a pennywhistle from Paddy Moloney of the Chieftains, an old Irish flute from Matt Molloy of the Chieftains, and a flute from Ian Anderson of Jethro Tull. On February 15, 2011, she played one of the instruments live from orbit on National Public Radio. On April 12, 2011, she played live through video link for the audience of Jethro Tull's show in Russia in honour of the 50th anniversary of Yuri Gagarin's flight. She played the duet from orbit while Anderson played on the ground in Russia. On May 13 of that year, Coleman delivered a taped commencement address to the class of 2011 at the University of Massachusetts Amherst.
As do many other astronauts, Coleman holds an amateur radio license (callsign: KC5ZTH).
As of 2015, she is also a member of the board of directors for the Hollywood Science Fiction Museum.
As of 2015 she is also known to be working as a guest speaker in Baylor College of Medicine as a speaker for the kids program 'Saturday Morning Science'.