The war was instigated by the Covenant, whose High Prophets made a discovery which led them to believe that humans were directly related to the Forerunners in some regard, contradicting their interpretation of their ancient religion. Seeking to keep various political and religious orders intact, a holy war of genocide was declared against the human species and the discovery of their relation to the Forerunners was kept a secret. Over the next few decades the Covenant, with superior firepower, numbers and technology, would repeatedly overpower the UNSC across hundreds of worlds, including heavily defended strongholds such as Reach and eventually Earth. Humanity would win only scattered and costly victories.
The conflict was also the cause of the Great Schism within the Covenant. Forced to fight a war on two fronts, the formerly monolithic empire was torn apart. While the deciding battle of the war was fought on December 11, 2552, an informal ceasefire was not agreed upon until February 2553. The official cessation of hostilities was declared on March 3, 2553. The war was incredibly costly to both sides, with over twenty-three billion humans and billions of Covenant individuals killed during the hostilities. An outbreak of the virulent parasite known as the Flood almost consumed both factions near the war's end. The conflict lasted for a total of twenty-eight years.
After the ceasefire was declared, the Great Schism continued in the form of wars between the Sangheili and the Jiralhanae until at least 2559. Concurrent to this, the Sangheili species fell into a civil war, as did the Jiralhanae, while the UNSC itself had to deal with a resurgence in insurrectionist rebels, unsatisfied with the war's outcome. In the wake of the Covenant's cessation, its former member species fragmented into many splinter factions. Among the most notable of these groups was the religiously devout new Covenant formed in the disarray following the war by Shipmaster Jul 'Mdama. The UNSC was still locked in conflict with this faction, along with several other splinter groups in, until late 2558.