Four years, seven months, and ten days after the events of Halo 3, a mysterious energy passes through the aft section of the UNSC Forward Unto Dawn. Cortana activates John-117's cryopod as an unknown assailant boards the ship. After progressing through part of the ship the assailant turns out to be the Covenant, to which Cortana expresses concern as she believed that humanity had a cease fire with the Sangheili. As John-117 fights his way through the Covenant boarders, it is revealed that it isn't one rogue Covenant ship on a salvage operation, but an entire fleet orbiting a Forerunner world. Cortana notices the nearest cruiser has it's shields down and suggests firing a tactical nuke at it. Immediately after the cruiser is destroyed, a passage into the planet opens and activates a gravity well that begins to pull every ship in. The already weakened Forward Unto Dawn starts to disintegrate as it passes into the planet. While making their way to the escape pods, Cortana starts acting erratically. However upon reaching the pods, a Covenant cruiser collides with the Dawn, tearing through the escape pods. The hull breach sucks the Spartan outside just as the wreckage passes through.
John-117 awakens to find himself inside the planet. Cortana reveals her behavioral problem is due to her going into the first stages of Rampancy. John-117 suggests trying to find a ship back to Earth to see if Dr. Halsey, Cortana's creator, can fix her condition. Eventually they fight their way through Covenant forces to a localized Cartographer. Cortana says that the only intel she can get is that their location is a shield world called Requiem. She also receives a signal from an unknown source that is definitely "not Covenant" in origin, and suggests looking for the signal. They find that the mysterious signal is being bounced off of a tower near the planet's core, Cortana opens a portal as close as possible to the core just as a large number of a new type of foe appears.
After being teleported closer to the signal it is revealed the signal is from the UNSC Infinity asking for help. A satellite near the center of the planet is blocking the signal, where two jamming towers are boosting the signal blocking device's power. Cortana suggests taking these jamming towers down to receive the whole signal. After defeating several groups of the unknown enemy, the only intelligence Cortana is able to get on them is the word "Promethean", and that they appear to be more advanced combat AIs than Sentinels. After taking down the first tower it is revealed the Covenant is very interested in finding something inside the core. After the second tower is downed the full signal of the Infinity is received. After discovering the ship is going to enter the planet, Cortana attempts to warn them away but is still unable to get through. Fighting their way to the center of the Satellite the pair discover a spherical object - the source of the signal. After attempting to stop the signal the sphere comes close to John's location where part of the sphere comes out of the bottom. A sole figure is seen on a pedestal. The unknown figure reveals himself to be The Didact, and handily defeats John-117 before declaring that his people, The Forerunners themselves, are returning to the Galaxy after thousands of years, and he remarks on how Humanity must still be weak, as the Covenant do not answer to Humanity and therefore are still unworthy of the Mantle.
John manages to escape the Didact and makes his way to the Infinity, which had entered the planet. The Didact also heads for the Infinity. After fighting off many Prometheans and Covenant, who have joined forces, he finds Commander Thomas Lasky, Spartan Commander Palmer and scattered groups of Marines. Chief clears an LZ for a Pelican to pick them up, and is transported to the Infinity, where he fights off waves of Covenant. Then, he is introduced to Captain Andrew Del Rio and Commander Palmer. Palmer, Lasky, and John are sent on a mission to allow the Infinity to escape Requiem, and are given a Mammoth. After destroying many Covenant vehicles, including a Lich, the mission brings John inside what is assumed to be a trap. It turns out not to be when John and Cortana are separately taken by the Librarian, who explains that the Prometheans were once Humans, and how the Didact is looking to escape Requiem and find the Composer, which he plans to turn on humanity. She helps to accelerate Chief's 'evolution' so that he can survive the Composer. Once John and Cortana are reunited, they proceed outside of the Forerunner structures, where they attempt (and fail) to destroy the Didact. They are returned to the Infinity, where Del Rio gives the command to leave Requiem; stating that they should return to Earth and inform FLEETCOM about what had occurred. Cortana and John attempt to convince him otherwise, but the Captain orders that Cortana be decommissioned due to rampancy. Upon Chief's refusal to hand her over, he orders both Palmer and Lasky to arrest him, but neither of them move. With Lasky's assistance, John escapes the Infinity before it leaves and attempts to destroy the Didact once and for all. However, he is unsuccessful, and hides inside a Lich to follow the Didact into slipspace.
He, along with The Didact and a Covenant fleet, arrive at Halo Installation 03, where the Covenant under the Didact's control immediately attack the UNSC science facility orbiting the Halo, that housed the Composer. After fighting his way inside, John argues with some professors there and grabs a HAVOK bomb to attempt to destroy the Composer. Unfortunately, he is too late, and the Composer is fired and kills all on the base aside from him. He takes a Broadsword to follow the Didact to Earth, where he is assisted by the Infinity, which is now controlled by Commander Lasky, in getting inside. There, the Didact fires the Composer, and extermination of Humanity begins in New Phoenix. In order to bring down the Didact's shields, Cortana clones her rampant personalities to overload the system. John places her chip in a holopedestal, but it is destroyed, and she is brought into the Composer's system. She manages to weakly communicate with John before assisting him in killing the Didact and destroying the Composer. She uses the last of her energy to form herself into a visible form and touches John for the first and last time. She dies right before the Composer collapses around them. John is found amongst the space debris by a Pelican. Talking with John, Commander Lasky echoes a statement Cortana once made to John regarding the humanity of soldiers. John is seen on Infinity's Spartan deck, having his armor removed.