Krantz’s specialty as a researcher and teacher included all aspects of human evolution, but he was best known outside of academia as the first serious academic to devote his professional energies to the scientific study of bigfoot. His studies of bigfoot (which he called "Sasquatch," after the purported native term) led him to theorize that this was an actual creature; specifically, a surviving population of gigantopithecines. He was a defender of the authenticity of the Patterson-Gimlin film and a variety of casts collected by Paul Freeman and Ivan Marx.

Krantz was also drawn into the Kennewick Man controversy, arguing both in academia and in court that direct lineage to extant human populations could not be demonstrated.

Krantz died in 2002 from pancreatic cancer in his Port Angeles, Washington home. At his request, there was no funeral. Instead, his body was shipped to the University of Tennessee's body farm, where scientists study human decay rates to aid in forensic investigations.

In 2003, his skeleton arrived at the Smithsonian's Museum of Natural History and was laid in its final resting place in a green cabinet, alongside the bones of his three favorite wolfhounds, as was his last request.