The Prothean War

The Protheans' belief that they could hold their own against machine intelligence was shattered with the arrival of the Reapers
 in approximately 48,000 BCE, who were far more advanced than the
machines the Protheans had been battling. They were caught completely
off-guard by the scale and rapidity of the assault. The Reapers entered
the galaxy through the Citadel, instantly decapitating the Protheans'
government and disrupting the mass relay network, isolating Prothean
systems from one another. Worse, records on the Citadel provided the
Reapers with access to all of the Protheans' census data and star
charts, allowing them to effectively track every Prothean in the galaxy.

The Protheans' greatest strength, their unified empire, proved to be
their downfall. As the Protheans were united under the leadership of a
single governing species with a series of subordinate races, the Reapers
 were able to quickly undermine the Prothean hierarchy and cause
Prothean forces to become scattered when their ruling body had been
compromised. In addition, as all the races within the Empire conformed
to a single military doctrine, they proved unable to adapt when the
Reapers identified and exploited their weaknesses.

While their domain crumbled, the Protheans were powerless to
defend other races from the Reapers' predations. They ceased all study
of primitive species in the hope that the Reapers would deem them too
primitive for harvest. It was hoped that some Protheans would survive
the Reapers' purge and go on to unite these species to create a new
empire. The Protheans' primitive subjects survived and went on to become
 the present cycle's dominant ones. Other races subjugated under them,
however, weren't as lucky.

The densorin,
 a race who had mastered sciences beyond even the Protheans'
understanding, attempted to pacify the Reapers by sacrificing their
children to them, but this only allowed the Reapers to destroy them more
 quickly. The zha'til,
 symbiotic AIs that had been created by a race called the zha to keep
themselves alive on their dying homeworld, were subjugated by the
Reapers and formed hostile mechanical swarms. They became such a threat
that the Protheans were forced to obliterate the zha'til entirely by
sending the star of the zha's home system into supernova.

Over the next several centuries, the Protheans fought the Reapers
from system to system, world to world, and city to city. If necessary,
whole colonies were sacrificed and abandoned to the Reapers; while the
Reapers concentrated on subsuming the inhabitants of those colonies, the
 Protheans had time to regroup. In the long run, however, this strategy
was extremely costly, depriving the remaining Protheans of whatever
infrastructure and manpower they had given up. Inexorably, the Reapers
conquered, enslaved, or destroyed Prothean-controlled planets. Growing
desperate, some Protheans made repeated offers of surrender to the
Reapers, but these were always met with silence.

In
 addition to the overt threat of the Reapers, the Protheans had to
increasingly deal with enemies from within their own ranks. Indoctrinated
 Protheans acted as sleeper agents for the Reapers, infiltrating and
swiftly betraying their own kind and revealing the Protheans' dwindling
hiding places and carefully-laid plans to survive the destruction.

At some point the Protheans learned of the cycles of galactic
destruction through studying the ruins of other extinguished
civilizations. Plans for the Crucible,
 which was based on designs left behind by previous civilizations, were
discovered, and the Protheans set about to building one of their own. In
 the course of the Crucible's construction, some Protheans came to
believe that the Reapers could be controlled with the device, but
inevitably fell prey to indoctrination as well in their attempts to
harness Reaper technology. They sabotaged the Crucible, robbing the
Protheans of their last hope to defeat the Reapers.

After centuries of careful, systematic work, the Reapers had
killed or enslaved every Prothean in the galaxy, and stripped their
worlds of resources. Removing all traces of their presence, the Reapers
then retreated through the Citadel into dark space and sealed it behind them.