The game begins with Lara setting out on her first expedition aboard the ship Endurance, with the intention of finding the lost kingdom of Yamatai. By her suggestion and against Whitman's advice, the expedition ventures into the Dragon's Triangle, east of Japan. The ship is struck by a violent storm and shipwrecked, leaving the survivors stranded on an isolated island. Lara is separated from the others and captured by a strange, savage man. She manages to escape while her captor is killed as the cave collapses due to her actions. As Lara tries to locate the other survivors, she finds more evidence that the island is inhabited, such as strange carvings, dead bodies, and animal sacrifices. She eventually finds her friend Sam and a man called Mathias, who claims to be a teacher who was shipwrecked on the island. As Sam tells Mathias the legends of Himiko, Lara passes out; when she wakes, Mathias and Sam are nowhere in sight.
When Lara regroups with the other survivors, Whitman decides to go with Lara and search for the still-missing Roth, while the rest of the group (Reyes, Jonah, Alex and Grim) set out to find Sam and Mathias. As Lara and Whitman explore, they discover that the island's inhabitants are worshipping Himiko, confirming that the island is Yamatai. Upon discovering a shrine erected in Himiko's name, they are captured by the islanders and taken to a settlement along with several other survivors from the Endurance. When the survivors attempt an escape, the captors turn on them. Lara is separated from Whitman and tries to hide, but is found by one of the islanders and forced to kill him. She fights off the remainder of the attackers and reunites with Roth, saving him from a wolf attack.
Lara manages to activate a radio tower and call for help, but the plane that answers the call is struck by a freak storm, and Lara hears a mysterious voice saying "No one leaves" in Japanese. Unable to save the surviving pilots, Lara is contacted by Alex and Reyes, who reveal that Sam has been kidnapped by the islanders, a violent cult known as the Solarii Brotherhood. Lara tries to rescue her, but is stopped by Mathias, leader of the Solarii, and ordered killed: she is saved by an attack from samurai-like Oni. Escaping the ancient monastery where she is taken by the Oni, she hears from Sam that Mathias is going to put her through the "Ascension", a "fire ritual" to find the next Sun Queen that will burn her to death if it is unsuccessful. Lara follows them to the Solarii fortress and is aided by Grim.
The Solarii take Grim hostage, but he sacrifices himself to so Lara can escape. With Roth's aid, Lara infiltrates the fortress and sees the ritual begin. When the fires are lit, a great wind blows them out, showing Sam to be the next Sun Queen. Lara escapes again and reunites with her friends, forming a plan to rescue Sam and escape. Aided by Whitmanwho has managed to negotiate some degree of freedom with the SolariiLara returns to the palace to rescue Sam as Roth commandeers a helicopter to get them out. Lara succeeds, but persuades Sam to escape by land when she sees another storm gathering as the helicopter approaches. As Lara tries to force the helicopter pilot to land, they are brought down, with Lara nearly dying. Roth revives Lara, then takes a fatal blow from Mathias meant for Lara. While mourning Roth, Lara accepts that the storms are not natural, but are somehow connected to the Sun Queen and designed to prevent anyone from leaving the island.
She meets up with the other survivors, who have evaded the Solarii long enough to secure a boat for escaping the island, provided that it can be repaired. They are joined by Whitman, who claims to have escaped, though Lara begins to suspect him of working with the cultists. Lara and Alex find parts for the boat in the wreck of the Endurance. They come under attack by the Solarii and Alex triggers an explosion, sacrificing himself so that Lara can escape with the tools. Finding an account of a World War II-era Japanese military and Nazi scientific expedition to the island that sought a way to harness the storms as a weapon, Lara decides to explore a coastal tomb, where she finds the remains of a samurai general who committed seppuku.
It is revealed in a message he left that he led the Queen's Stormguard, the Oni that defend the monastery, and that the Queen's successor took her own life rather than receive the Sun Queen's power, leaving the Sun Queen trapped in her body after death, and her rage has manifested as the storms. Lara realises that the Ascension is not a ceremony to crown a new queen, but rather a ritual that transfers the original Sun Queen's soul into a new body: Himiko's spirit wants to escape its current body, and Mathias plans to offer Sam as a new host.
Lara returns to the survivors on the beach to find that Whitman has betrayed them, abducting Sam and handing her over to Mathias. Lara, Jonah and Reyes give chase, heading up a river to the monastery, with Lara arriving just in time to see Whitman killed by the Oni. After fighting her way through the Solarii and the Stormguard, Lara arrives at the top of the monastery where Mathias is performing the Ascension ritual. Lara kills Mathias when she shoots him from the roof of the monastery, before destroying Himiko's remains to save Sam. With the storms dispersed, Lara, Sam, Reyes and Jonah leave the island and are picked up by a cargo ship. As she and her friends sail home, Lara decides that there are many more myths to be found and resolves to uncover them, stating that she isn't returning home just yet.