The first iteration was published by the United States Department of Transportation (USDOT) in December 1973, as Emergency Services Guide for Selected Hazardous Materials.

[2] A revised version would be released in January 1977, which added an image of the relevant, newly adopted hazardous material placards to each substance's entry.

Placard charts for devising responses when the exact substances isn't known and Chemtrec as an advice resource would also make their first appearances in 1980.

[7] The 1996 edition would be a turning point, released as North American Emergency Response Guidebook, this edition would see formal involvement of Transport Canada (TC) and he Secretariat of Communications and Transportation (SCT) of Mexico for the first time, with their national emblems appearing alongside the USDOT logo and contact information in the rear of the book.

[12] It is primarily a guide to aid first responders in quickly identifying the specific or generic hazards of the material(s) involved in the incident, and protecting themselves and the general public during the initial response phase of the incident.The Emergency Response Guide is intended to give first responders (firefighters, police officers) prompt advice during the initial stages of an emergency, such as a fire or chemical leak resulting from a transportation accident, such as a train derailment or crash involving a truck.

It has been translated in to a number of other languages by third parties, including Mandarin, German, Hebrew, Japanese, Portuguese, Korean, Hungarian, Polish, Turkish and Thai.

Each of the 62 guides provides safety recommendations and directions on how to proceed during the initial response phase (first thirty minutes) of the incident.

For example, "the material gives off irritating vapors, easily ignited by heat, reactive with water"; "highly toxic, may be fatal if inhaled, swallowed or absorbed through skin"; etc.

It also includes information on fighting fires (example, do not apply water to sodium), warnings for spills or leaks, and special directions for first aid (example, not to give mouth-to-mouth resuscitation if the materials are toxic).

The other, is Guide #111 - Mixed Load/Unidentified Cargo, which is for use in situations where either multiple hazardous materials are involved, or even basic information is unavailable, such as when a railcar or truck is buried under vehicles/debris or obscured by fire or smoke.