After the many battles that had shaken the Khans eventually led to their seemingly ultimate defeat, the survivors refused to give up their pride and heritage. From this point the Khans dispersed into the world to begin anew. While it is not known what happened to the other groups, the group that settled in the Mojave quickly became one of its major players. Creating multiple settlements the Khans soon began raiding the other tribals of the surrounding area, as well as the few settlers that began to come from the New California Republic, who were considered both intruders and easy targets. However, it was not long before Mr. House, the ruler of New Vegas, finally recovered his systems from the nuclear bombs that he could not shoot down. House quickly tried to resolve the conflicts by offering the tribes their own Casino to operate under him, but the Great Khans already owned a large amount of land and refused to give up their heritage and follow House's orders.
Knowing the Great Khans were his greatest threat not only because of their violence, but also because their hostility towards the factions of the Mojave could potentially hurt his plans for Hoover Dam, Mr. House gave the tribes that surrendered to him (the Chairmen, the White Glove Society, and the Omertas) large supplies of guns and ammunition as well as what little securitron assistance he could offer at that time, and prepared for war. These tribes, aided by House, drove the Khans out of the northern Mojave, pushing them out of the area around New Vegas and ending their time of power. It wasn't long after these wars that the NCR arrived from the south. They had come on a mission to annex New Vegas from whatever tribals were holding it, and to secure Hoover Dam as a power source, all under the initial guise of hunting down the Great Khans in retaliation for attacking their settlers. The Great Khans were now in no shape to fight, but the NCR killed them on sight out of revenge, leading to the first real spark of the resentment to the NCR held by the Great Khans. The Great Khans resumed their raiding of NCR caravans and settlers, as well as attacking the soldiers, who were poorly armed and demoralized. Initially, the Great Khans believed House would attack as well, so they took a very hard-line stance with the NCR in belief that they would be expelled from the Mojave very soon. However, House had been waiting for a strong, negotiable faction like the NCR. After the NCR secured Hoover Dam and Helios One from the Brotherhood of Steel, House freely gave them the territory, as long as the strip was given 5% of its energy output. This turn of events meant certain death for the Great Khans, who now had to fight alone against the full force of the NCR.
It wasn't long before the NCR had burnt down their settlements, killed most of their people, and forced them into hiding in the valley-settlement of Bitter Springs. In an infamous operation, the NCR sent the 1st Recon on Coyote Tail Ridge, near the mouth of the gorge that held Bitter Springs within, and ordered them to fire on anyone trying to escape as the large main force charged in from multiple points. While the NCR initially thought this was a military base, they were dead wrong. Bitter Springs was a settlement filled with the sick, elderly, children, and others who were unable to fight, while the actual soldiers were in war parties elsewhere. Due to this misinformation, the snipers and soldiers assaulting the settlement, who were under orders to shoot on sight, slaughtered countless innocent people in a move that would shame the NCR for years to come. Due to the low amount of actual soldiers protecting Bitter Springs, the NCR quickly defeated the Great Khans. With no home, and with the NCR on their tail, the Khans took their few survivors and created a camp at Red Rock Canyon.
Most of the residents in the camp were the soldiers who were on the warpath during the Bitter Springs Massacre, and because of the large number of Khans concentrated there, as well as its strategic position, the NCR could not decide on how to assault them. Eventually, the NCR declared their victory over the Great Khans, ending the war between them, and turned their attention to other things, such as raiders and diplomacy with House. The Great Khans, however, were still a threat. Now armed with a deeper resentment for the NCR then ever before, the Khans slowly regained their strength, biding their time until the NCR can be attacked once again, and allying themselves with any enemy of the NCR, such as Caesar's Legion and the Fiends. Soon after their arrival in Red Rock Canyon, the Followers of the Apocalypse offered them medical assistance and access to knowledge via missionaries. While the Great Khans initially used their good-will to assist those wounded in Bitter Springs, they soon learned how to make their own chemical compounds and medicines, making them more self-efficient. The Great Khans soon learned how to make psycho-active and addictive narcotics with incredible skill. Before this they had been using coyote tobacco chew and other natural plants, and according to Bitter-Root, a survivor of Bitter Springs who actually joined the NCR unit that killed his family, they were addicted to these plants before they had even learned how to make synthetic narcotics. These new chemical narcotics lead to many Great Khans becoming addicts, changing them dramatically. The Great Khans soon became the leaders of the drug trade, selling their wares illegally to the Crimson Caravan and other NCR traders looking for profit, as well as selling these drugs frequently to the Fiends to keep them constantly high, so they could harass NCR patrols.
Their leader, Papa Khan, sensing a great battle coming, attempts to become allies with Caesar's Legion out of pure spite and hate for the NCR, which is made obvious by Caesar's Legions zero-tolerance outlook on drugs and medicine, as well as Caesar's Legion hate for any and all factions that are not under their rule. Regis, Papa Khan's advisor and head enforcer, sees these signs, and views the alliance as a last ditch attempt to hurt the NCR, also believing that Caesar's Legion will destroy the Great Khans when the battle is over. However, Caesar sends a frumentarii diplomat named Karl to advise the Legion's new temporary allies. Karl soon discovers who the advisors are among the Khans, and quickly quells any idea of dissent by promising various things to the soldiers, as well as complementing them on their strength. Karl convinces the women, who would be enslaved under the Legion, that they may become soldiers in the Legion, and promises the Khans amnesty from the Legion, free trade of drugs, and all of the land West of the Mojave. However these promises are all lies used to convince the Khan's that the allegiance with Caesar's Legion is legitimate.