343 Guilty Spark

When the game begins, John-117 is back on Earth, where the Covenant loyalists (Brutes, Drones, Grunts, Hunters and Jackals), led by the Prophet of Truth, have laid waste to most of the planet.
Humankind's population has been reduced to a mere 200 million, and is backed against the wall, fighting for its very survival. The only reason humans have made it this long is that the Covenant is preoccupied by an excavation site a few miles from the ruins of New Mombasa, where they have uncovered a massive Forerunner structure (seen in the E3 2006 trailer), buried under the planet's surface for thousands, if not millions of years.

Sergeant Major Johnson and the Arbiter retrieve the Master Chief from a hasty jump from orbit, landing in the east African jungle.
The three of them manage to make it to Crow's Nest, a 21st century facility used as a local base of operations by the UNSC. Shortly after they reach their destination, the Covenant mounts an attack on the facility, and it is during this time that the Chief starts receiving disturbing transmissions from Cortana.
After a brief struggle, in which the outpost is lost, Master Chief receives orders from Commander Keyes and Lord Hood to clear a way into the African city of Voi, and destroy all anti-air Covenant defenses in preparation for an all-out assault on Truth and the artifact.
After the Master Chief and the Arbiter destroy the defenses, Truth activates the artifact and creates an enormous Slipspace portal, into which all the Covenant ships retreat.
As Keyes follows the Dreadnought a Covenant ship controlled by the Flood arrives by slipspace and crash lands nearby, and the parasite quickly spreads throughout the city.

The Master Chief and the Arbiter attempt to fight off the Flood and retrieve a recording of Cortana from the Flood ship. After they have completed all of their objectives, Guilty Spark arrives by an Elite drop-ship. Once the Arbiter and Master Chief are evacuated, the remaining Covenant fleet proceeds to glass the parts of Africa that have been infected. This amplifies the hard feelings between Lord Hood and Shipmaster Rtas 'Vadum, the Spec. Ops Leader of Halo 2 and new leader of the elites. Once the Elites and Lord Hood decide to follow Truth, the remaining Elite ships - approximately 9 and 3 UNSC Frigates leave Earth via the slip-space portal and find themselves near an immense artificial structure, (where they engaged a fleet 3 times their size and won) which is soon revealed to be the Ark. They find that the Ark is in fact positioned outside of the Milky Way galaxy, just beyond the Halo rings' effective firing range. Guided by Guilty Spark and temporarily assisted by the Flood, the Chief and the Arbiter push their way to one of the communication arrays of the Ark, where they barely manage to stop The Prophet of Truth from activating the rings. Commander Keyes dies as she tries to kill herself and Sergeant Johnson to stop Truth from activating the rings.

In the meantime, a flood-infested High Charity arrives by Slipspace jump.
After executing The Prophet of Truth, the Arbiter and the Master Chief discover that a replacement ring has been constructed by the Ark to replace the one destroyed by Master Chief. The Chief decides to activate the ring so as to destroy any chance the Flood has from spreading even further. However, the Chief and the Arbiter first take a detour through High Charity to recover Cortana, who, under the grasp of Gravemind, had the activation Index for the replacement Halo. After rescuing the AI, they destroy the Covenant home world as they make their escape, which seemingly kills Gravemind.

When they arrive on the newly built Halo, they quickly discover that Gravemind is still alive, and attempting to reconstruct itself on the new Halo.
The Chief, Arbiter, and Sergeant Johnson quickly make their way to the control room, where they attempt to fire Halo. Guilty Spark realizes that this will destroy his new ring because it is not fully ready yet, and kills Sergeant Johnson as he tries to activate the ring. Master Chief destroys Guilty Spark, activates the ring, and barely manages to escape with the Arbiter on Forward Unto Dawn, a UNSC frigate ship.

Back on Earth (March 3, 2553), a memorial service is held for fallen UNSC personnel. A memorial has been constructed from part of a spaceship, atop a hillside which Lord Hood orders will "remain barren". Affixed to the memorial are flowers, photos, and messages. Among the images seen on the memorial are that of Miranda Keyes and A. J. Johnson. After the service, Hood tells the Arbiter that although "I remember how this war started, what your kind did to mine.
...I can never forgive you, but...you have my thanks for sticking by him until the end. Hard to believe he's dead.". The Arbiter then replies, "Were it so easy".
It is implied that John did not survive to make it back to Earth. Following this, the Arbiter and Shipmaster depart, bound for the Elite homeworld above a Covenant cruiser. Further alluding to Master Chief's death is the numbers "117" scratched into the space ship fragment, next to the insignia of a Naval Master Chief Petty Officer (John 117's rank) if read correctly it says Master Chief 117.

After the credit roll, footage is shown of the Master Chief and Cortana on-board the rear section of Forward Unto Dawn, which had apparently torn off during the slip-space jump; the pair are drifting through space. Cortana tells John she will drop a distress beacon, but that it could be years before they are found.
The Chief makes it to a cryotube, and as he is climbing in Cortana comments "I'll miss you". He replies "Wake me when you need me".

If the game is completed on the Legendary difficulty, the section of
Forward Unto Dawn that Cortana and the Chief are aboard is seen drifting towards an artificial looking planet after an unknown amount of time since he put himself in cyro. A galaxy cluster is seen in the background, leading many to believe this is the Milky Way, but as the universe has many galaxies within it, there are many possibilities as to the identity of the planet. This, however, is unlikely as Cortana stated that only part of the ship made it through the portal.
It is more likely that the planet is outside the galaxy and within traveling distance of the Ark. It has been speculated that it is the Forerunner home world as their home world would be outside the range of the Halo pulses and the Terminals did refer to a Forerunner home being some distance from Earth. It also appears that the wreckage is in the Iris Nebula.

This ending draws an interesting parallel with the opening scene of Marathon, leading some to jump to conclusions and say that Halo 3 is in fact a direct prequel to Marathon. However, Bungie has on several occasions stated that Marathon and Halo do not occur in the same universe.