The Quelling of the Protheans was a war between the Protheans and The Reapers. The Protheans were almost wiped out as a result of this war, and the few surviving members of the race were forced into hiding.
The Reapers attacked using their usual tactics of the epic revelation that the center of Government is actually a big teleporter, followed by a mass transportation, then stealing navigation data for every planet, than attacking them all in turn.
The Protheans were too busy snacking on Grunt Bladder and Forerunner Intestine that they didn't even notice the Reapers were attacking until it was too late.
Despite this event, which happened 50,000 years ago, Protheans and Reapers in the present day enjoy cool, if tense, diplomatic relations.