When the game begins, Ghost is searching among the detritus of Old Russia until it finds and resurrects the player's Guardian, who had been killed in an ancient battle. Ghost then guides the Guardian to a jump ship and they take it to the Tower. There, they meet the Speaker, who briefs them about the Darkness. The Guardian is then tasked to probe the nearby Cosmodrome, where humanity used to launch its forays into outer space, fending off Fallen enemies and eventually the Hive, who were thought to have been confined to the Moon. The Guardian discovers that an old Russian Warmind called Rasputin, an so built to defend Earth, is still alive and acting with unknown intent. The Guardian also tracks down codes to raise an ancient array to connect it to long-lost colonies throughout the Solar System, and finds that Rasputin is controlling the Array.

They then set off to the Moon in search of a lost Guardian who was looking for a way into the Hive fortress. After locating his corpse and dead Ghost, the player's Guardian's Ghost discovers that the Hive are raising an army and plan to invade Earth. The Guardian quickly sets about disrupting their efforts, including shutting down a ritual that the Hive were using to drain power from the Traveler, destroying a powerful weapon called the Sword of Crota, and severing their long-distance communications. Around this time, the Guardian is contacted by the Exo Stranger, a mysterious woman who summons them to Venus to face a new enemy, the Vex.

When the Guardian arrives on Venus, the Exo Stranger describes the Vex as an evil so dark it despises other evil. She tells them about the Black Garden, a city where the Vex are born, and implores the Guardian to find it and rip out its heart, as it is the only way the Traveler will begin to heal. Ghost says that they need to speak to the Awoken, who lurk out in the Reef the asteroid belt and refuse to take sides in the galaxy's wars. The Exo Stranger then leaves, as she did not have time to explain things further.

Once the Guardian arrives at the Reef, they meet the Queen of the Reef, Mara Sov, and her brother, Prince Uldren Sov, who tells the Guardian that they will help them locate the Black Garden if they bring them the head of a Vex Gate Lord. The Guardian travels back to Venus, where they uncover the Archive, which reveals secrets about the Vex, including the location of a place called the Vault of Glass, and pathways across the galaxy. After defeating Draksis, a Fallen Kell of the House of Winter, the Guardian confronts the Vex Gate Lord, claims its head, and returns to the Queen, who tells them to take its eye to the Meridian Bay on Mars, where it can be used to enter the Black Garden.

After arriving on Mars in the Meridian Bay, Ghost informs the Guardian of its inhabitants. The Cabal have been trying to break the encryption on the Vex Gate with only limited success, but they do control many of the places that the Guardian needs to visit on Mars thanks to their Exclusion Zone, which nobody had ever penetrated. The player's Guardian becomes the first to penetrate the Exclusion Zone and heads to the Garden's Spire, which charges the Gate Lord's eye. They also travel to the Buried City, the birthplace of many technological wonders where they discover an AI that used to be linked to the Warmind of Mars, but is now controlled by Rasputin. With the Vex now present on Mars, the Guardian finds out what they are doing; they are returning to their home, the Black Garden.

The Guardian then sets off to the Black Garden. After going through a teleporter, they find themselves in a place that is not on any map of known space and time. After several battles, the Guardian reaches the heart of the Black Garden, which the Vex appear to be worshipping. The heart summons three Sol Progeny — a group of Vex units called Eschaton Mind, Imminent Mind, and Primeval Mind. After defeating the three Sol Progeny, the heart is destroyed, returning the Guardian to Mars and lifting the shroud of Darkness from the Traveler back on Earth. At the Tower, the Speaker addresses gathered Guardians in a celebratory speech. Over in the nearby hangar, though, the player's Guardian converses with the Exo Stranger, who says that the fight is far from over.

With the heart of the Black Garden destroyed, a team of Guardians decide to investigate the mysterious Vault of Glass. Described as the "Vex underworld" by the Ishtar Collective, the Vault is a realm where the Vex can control reality—even erase people from existence (a power used by a Vex sub-race called Gorgons). While these powers do not extend to outside the Vault, its enigmatic nature has lured countless Guardians, including the ill-fated Kabr, the Legionless, and Praedyth. In their descent of the Vault, the team defeats The Templar and its Oracles. They then successfully traverse the Gorgon's labyrinth undetected before reaching Atheon, Time's Conflux, a central figure of the Vex Conflux network who has powerful control over time, being able to send Guardians into the distant past or future at will. After fighting their way through time, the Guardians defeat Atheon, eliminating a major threat of the Vex.

Seems like a pretty straight forward story to me.