Before Mass Effect 2, nothing was known about the Collectors' origins except that they resided beyond the Omega-4 mass relay. It would later be discovered by the crew of the Normandy SR-2 that the Collectors were in fact created by the Reapers 50,000 years ago when they harvested the legendary Prothean race. Just as the Reapers had recently turned humans into cybernetic Husks, so had they done to the Protheans and created an army of cyborg monsters indoctrinated to their will. Over the millennia, the Collectors had observed and studied the development of organic cultures remaining from the Prothean cycle. Based on a space station located near the galactic core, they would often venture forth from the Omega-4 relay to trade with different races, offering samples of their technology in exchange for unique genetic material. This would continue until near the end of the 50,000-year cycle when the Reapers' next invasion was postponed thanks to the actions of the Human Alliance officer, Commander Shepard, who had destroyed the Reaper vanguard Sovereign.
Recognizing Shepard as a threat to the Reapers and the potential the Commander's species possessed, the Collectors launched an attack against the SSV Normandy and destroyed it, supposedly killing the Commander in the process. The Collectors then began the premature harvesting of the human race by attacking their colonies out in the Terminus Systems. With each attack, the colony itself remained intact, but all citizens were abducted. For two years, entire colonies would be emptied of their inhabitants, their fates left uncertain. When Cerberus began investigating the abductions after ressurrecting Commander Shepard, it was discovered that the Collectors were originally Protheans that had been transformed by the Reapers; their bodies completely reconstructed with cybernetics and their race sustained through centuries of controlled cloning procedures. During Shepard's investigation, the Collectors' mission was made apparent: they intended to target every human world in the galaxy and harvest humanity before the Reapers' next invasion. When the Collector base was discovered, the Normandy crew witnessed first-hand exactly why the Reapers harvested organics: the humans the Collectors had abducted were being processed and broken down into raw genetic material and used to create a new Reaper, one with clear human features.
When the Normandy attacked the Collectors' base, they destroyed the Human-Reaper larva being created and were able to sabotage the base. Shepard's actions are determined by the player at this point and it is left up to the player to decide whether Shepard destroys the Collector base by overloading its power core, or reconfiguring the explosive mechanism into a radiation bomb that would leave the base's technology intact, but kill off the Collectors themselves. Cerberus' director, the Illusive Man, recommends saving the base in order for Cerberus to use its tech to forward their goal of humanity's domination of the galaxy. Regardless of the choice the player makes, the Collectors are all exterminated.