Reichs studied anthropology at American University, earning a B.A. in 1971. She then received an M.A. (1972) and a Ph.D. (1975) in physical anthropology from Northwestern University. She was an assistant professor at Northern Illinois University from 1974 until 1978, when she accepted a position at the University of North Carolina at Charlotte. She became a full professor in 1996. Reichs began consulting with the office of the chief medical examiner in North Carolina in the mid-1980s. She was certified by the American Board of Forensic Anthropology in 1986 and in 1988 began working part of each year at the Laboratoire de Sciences Judiciaires et de Médecine Légale in Quebec. She also taught at the FBI Academy in Quantico, Va. In 1999 she served as a consultant to the UN Tribunal on Genocide in Rwanda, and in 2001 she helped identify remains of victims of the September 11 attacks on the World Trade Center in New York City. Throughout her academic career, Reichs wrote numerous scholarly articles; she also edited three books on physical and forensic anthropology.

In the late 1980s Reichs wrote a novel, which was not published. She reworked the novel in the mid-1990s, salvaging only the main character, forensic anthropologist Temperance Brennan, from the earlier manuscript. In Brennan, Reichs created a memorable protagonist whose professional life paralleled her own. She gave meticulous accounts of Brennan's forensic investigations, details of which she sometimes culled from her own lab work. Scribner, the first publisher to receive the completed manuscript for Déjà Dead, signed Reichs to a $1.2 million, two-book deal. Déjà Dead won the 1997 Arthur Ellis Award for best first novel. Other novels in the series include Death du Jour (1999), Deadly Décisions (2000), Fatal Voyage (2001), Grave Secrets (2002), Bare Bones (2003), Monday Mourning (2004), Cross Bones (2005), Break No Bones (2006), Bones to Ashes (2007), and Devil Bones (2008).

The popularity of Reichs's books led to a television show, Bones, which premiered on the Fox network in 2005. Reichs consulted with the show's writers and was also a producer.