In Reign of Fire, based on the 2002 movie starring Matthew McConaughey, players have a choice of fighting for human survival against the onslaught of the dragons or trying to stop the human resistance as one of the fire-breathing beasts. The latter option is unlocked only after you successfully complete several human-based missions as a Kentucky Irregular under the leadership of Denton Van Zan, utilizing vehicles including a 4x4 jeep, fire truck, tank, or buggy. Playing as a dragon, you must unleash a rain of fire on the weapons of human resistance by spitting fireballs and breathing napalm.

The vehicle-based human arsenal consists of such diverse weapons as a light machine gun turret, a tank cannon, ground-to-air rockets, heat-seeking missiles, a water cannon, and water grenades. Human enemies range from young Jakyls, who try to ram vehicles, to swarms of giant napalm breathers looking to toast anything in sight. As a human, the dragons aren't the only concern, as failing to carry out the uncompromising Van Zan's mission orders will also land you in hot water, or worse. Dragons, in addition to their fire-based arsenal, can also pick up objects, like humans and vehicles, and use them as bombs.

Reign of Fire contains extras in the form of movie clips and Mad at Gravity's music video "Walk Away." The game features a radar-based HUD for both dragons and humans, with color-coded bars and gauges tracking various elements, such as targets, allies, ammunition, attack strength, stamina, health, and so forth, with a save game opportunity available at the end of each successfully completed level. A total of 16 missions are presented.