In the year 2001, a virus has killed 99.99% of the females on Earth. Various countries fight over each others quarantine zones, and end up engaging in nuclear war, destroying much of civilization. The few remaining females are held by gangs who have taken over small pieces of the world. The main character, Griffin Spade, had his fiancee Madison taken away from Queens, New York by the U.S. Government. Griffin ends up separated from his fiancee, and New York City is destroyed. He claims a tank for his own and sets out to cross America and find her, battling gangs as he reaches his goal. After surviving the ruins of New York City, Griffin heads westward gaining recruits in the countryside, Chicago, Las Vegas, and San Francisco.
On January 13, 2006, a Queenlord, Cassandra, is spying on Griffin Spade's family, telling her troops to kidnap Griffin's son Brandon and kill everyone else. Griffin and his army manage to push back the invaders, but Cassandra soon turns the tables by mind-controlling Griffin's own army. Griffin and Madison manage to escape San Francisco and begin chasing Cassandra across the United States, eventually cornering her in Washington D.C.. Cassandra, however, escapes with Brandon to Europe; Griffin and Madison follow. They build a new army there, and chase Cassandra through London, Paris and Berlin. While in Paris, they discover Cassandra released the virus in 2001 to kill every female on Earth who didn't have the power of The Edge. It is in Berlin where Griffin finally rescues Brandon. They make it back to San Francisco and push back another invasion by the Storm Ravens, and finally corner and defeat Cassandra on Alcatraz Island. The story ends with a cliffhanger; an unidentified magician finds Cassandra's body and speaks of a "chosen one" as he resurrects her.
The year 2001 had seen one worldwide terror after another. A highly potent virus, known as the X2 virus, was released from an unknown source. It quickly became apparent it targeted only females, and while there wasn’t a 100% chance all females would contract it, once they did they had no hope of survival. Most of the remaining women were herded into national quarantine zones to prevent the virus from spreading further. The virus burned out in the beginning of May, but by then over 99.1% of all women on Earth had succumbed to it.
In the aftermath of the virus, the male population, fearing for its survival, began forming gangs and tribes. Governments, fearing an uprising and the growing chaos, nuked major population centers.
After the governments collapsed, the battles continued and desperate forces made a scramble for anything they could find. Two such campaigns widely known in the years after the X2 virus were carried out by Griffin Spade: the first was a journey spanning the entirety of America, from a bombed-out New York City to San Francisco, California, to reclaim his wife; the second, five years later, took him back the way he came and farther, through Great Britain, France, and finally to Berlin, Germany to rescue his son.
- New York: Queens - This is the original location of the detonation of the nuclear bomb that went off. The city is in ruins and for a few minutes, the sky is red. Some of the buildings can't be destroyed, which can be aggravating. In Campaign mode, you have to destroy 5 tanks.
- New York: Queens Midtown Tunnel - This part you have to cross the tunnel and survive gun buddies and Urban Decay tanks. Only available on Campaign mode.
- New York: Times Square - This part of the city is also in ruins. It is larger than Queens, and also a lot of the buildings cannot be destroyed. In Campaign mode, you must destroy 15 tanks and survive.
- New York: Stranglehold Bridge (George Washington Bridge) - Urban Decay stronghold. - Filled with mines, tanks, a Goliath tank, and gun emplacements. Only available in Campaign mode.
- The Heartland: Rescue a Queenlord. - You must rescue a queen lord while being able to prevail from Goliath tanks, tanks, and gun emplacements. Only available in Campaign.
- Chicago: Lakeshore Drive - You must rescue a Queenlord from the Psycho Brigade and bring it back to your home base.
- Chicago: State Street - Escort two Queenlords to safety. You must rescue two Queenlords from the Psycho Brigade and Skull Riderz and bring them back to your home base.
- Armageddon Highway - entrance into the west. You must make it through tanks, gun emplacements, mines, and three Goliath tanks occupied by the Mech Maniax, Nuclear Knights, and Charlie Company. Only available in Campaign mode.
- Area 51 - Three Queenlords to rescue. - You must rescue three Queenlords from the gangs.
- Las Vegas: Fremont Street - headquarters of the Alliance. You must acquire three Queenlords in order to make it through.
- San Francisco: Crimson Gate Bridge (Golden Gate Bridge) - You have to make it through this heavily armed bridge while destroying tanks, gun emplacements, three Goliath tanks, and 6 huge gun emplacements. Only available in Campaign.
- San Francisco: The Wharf - You must obtain three Queenlords from the Aftershocks, Skull Riderz, and Dark Angels to pass this level.
- San Francisco: Q-Zone - Rescue Madison. This is the final level. You must destroy all the gun emplacements, tanks, and two Goliath tanks, and retrieve Madison from the Dark Angels and bring her to your base. Only available in Campaign.