The Ghost Adventures series was preceded by an independent documentary-style film of the same name, filmed in 2004 and produced by 4Reel Productions in 2006, which premiered on the SciFi Channel on July 25, 2007.

The original film focused on the trio's investigation of alleged paranormal activity in and around Virginia City, Nevada, including the Goldfield Hotel in Goldfield, Nevada, a location the crew later returned to during the series' fourth, fifth, and seventh seasons.

During investigations, the crew places X marks with black or gray tape at sites of alleged serious paranormal activity, then set up static night-vision cameras and get locked inside the location overnight to prevent 'audio contamination' and extraneous shadows.

Several cast members claim to have experienced spirit possessions on camera: Zak Bagans says he was possessed at the Preston School of Industry and at Poveglia Island in Italy, Nick Groff claims he was overtaken by a 'dark energy' at the Moon River Brewing Company, and Aaron Goodwin claims to have been 'under the influence of a dark spirit' at Bobby Mackey's Music World and the Winchester Mystery House.

Ghost Adventures, along with Ghost Hunters, is credited with helping popularize paranormal television and ghost hunting during its original run on the Travel Channel.

During the Halloween special 'Ghost Adventures Live,' broadcast from the Trans-Allegheny Lunatic Asylum on October 30, 2009, inventor Robert Bess claimed an EMF meter was violently knocked out of his hands by a paranormal force, but video review later showed he had actually thrown it himself; hosts Bagans and Groff concluded in a follow-up special that they could not attribute the incident to anything paranormal.

The show has spawned numerous spin-offs and related productions, including Ghost Adventures: Aftershocks, Where Are They Now?, Serial Killer Spirits, Screaming Room!, Quarantine (filmed during the 2020 COVID-19 pandemic inside Zak Bagans's Haunted Museum), Top 10, House Calls, Deadly Possessions, Demon House, and The Haunted Museum (co-created with horror filmmaker Eli Roth).

The Quarantine miniseries began filming its first episode, 'Perimeter of Fear,' at the start of Nevada's state COVID-19 lockdown on March 30, 2020, with the crew locked inside Zak Bagans's Haunted Museum for 10 days, investigating items including the Jack Kevorkian van room and a display of haunted dolls.