Two years after the events of previous game, Nathan Drake (Nolan North) and Victor "Sully"

Sullivan (Richard McGonagle) enter a pub in London to meet a man named Talbot (Robin Atkin
Downes), who is interested in purchasing Nate's ring belonging to his ancestor Sir Francis Drake.
The duo accuses Talbot of giving them counterfeit banknotes, and a fistfight ensues. Outside,
they are subdued by Talbot's cohort, Charlie Cutter (Graham McTavish), and Talbot's employer,
Katherine Marlowe (Rosalind Ayres), steals Drake's ring. Cutter shoots Nate and Sully.
A flashback shows that 20 years prior, the teenage Nate (Billy Unger) searches a museum
in Cartagena, Colombia, for the ring. He sees Sully, then unknown to him, working with Marlowe
to retrieve the ring. Although he steals Sully's wallet, the man recovers it, but Nate uses the ring
on a museum artifact. He is almost shot by Marlowe's henchmen, but Sully rescues him and
takes him on as his protege.
In the present, Nate and Sully have survived; Cutter is, in fact, their ally, who worked with them to
track down Marlowe. With the help of Chloe Frazer (Claudia Black), they trace Marlowe's car to
an underground library. They retrieve T. E. Lawrence's notebook and a map showing Francis
Drake's secret voyage to Arabia, where he was commissioned by Queen Elizabeth I and John
Dee to find the lost city of Ubar. Nate deduces that clues to Ubar's location lie in Crusader crypts
in a French chateau and a Syrian citadel. He and Sully locate the abandoned chateau in France.
They find one half of an amulet inside the crypt but are ambushed by Talbot and his men, who
take the amulet and set the chateau on fire. Nate and Sully escape.
In Syria, Nate and Sully meet Chloe and Cutter, who have learned that Marlowe is the head of the
same order to which Francis Drake belonged. The group finds the second crypt and the other half
of the amulet, revealing the location of the next clue, in Yemen. As they escape Marlowe's men,
Cutter breaks his leg. He and Chloe are forced to abandon the quest.
In Yemen, Nate's estranged wife Elena Fisher (Emily Rose) helps them locate an underground
tomb, where they discover the location of Ubar in the vast Rub' al Khali desert. Nate is shot with a
hallucinogenic dart and captured by Marlowe and Talbot. Marlowe has accumulated documents
concerning Nate's childhood; Nate took the name Drake while growing up in an orphanage after
his mother killed herself, and his father abandoned him. Marlowe threatens Nate for the Ubar
location. When Talbot learns of Sully's location, Nate escapes and chases Talbot through the city.
He is captured by Rameses, a pirate working for Marlowe, who interrogates him for information
about Iram of the Pillars and who claims to have captured Sully. Nate escapes and searches for
Sully on the pirates' captured cruise ship. He discovers that Rameses lied about having Sully and
detonates a grenade, sinking the ship. Nate escapes, and Rameses drowns.
Nate is washed ashore in Yemen. He reunites with Elena, who informs him that Sully was
captured by Marlowe's men and forced to lead them to Ubar. Nate sneaks onto a cargo plane due
to airdrop supplies to Marlowe's convoy but is discovered, and a shootout ensues, culminating in
an explosion that destroys the plane. He deploys a cargo pallet parachute and lands in the
desert.
Nate wanders in the desert, hallucinating from thirst. He is rescued by a troop led by a Bedouin,
Salim (TJ Ramini). Salim explains that Ubar was doomed by King Solomon thousands of years
ago when he imprisoned an evil Djinn in a vessel and cast it into the heart of the city. Salim and
Nate destroy Marlowe's convoy and rescue Sully. Nate and Sully lose Salim in a sand storm but
eventually find and open the gate to Ubar. In Ubar, Nate drinks from a water fountain. Talbot
appears with Marlowe and shoots Sully, killing him. Furious, Nate gives chase and encounters
more of Marlowe's men, who have been possessed by the Djinn. He experiences vivid
hallucinations and comes round, realizing he had a nightmare in which Sully was killed. Nate
realizes that King Solomon cast the vessel containing hallucinogenic minerals into the well
beneath Ubar, tainting the water and thus causing Nate to hallucinate. The vessel is what Queen
Elizabeth sent Francis Drake to find, but after learning the real reason behind his quest, Drake
abandoned his mission - he then lied to the Queen on returning to London, thus the game's
subtitle.
Nate and Sully find Marlowe, who is using a winch to recover the vessel from the waters. Sully is
nearly killed by Talbot, but Nate destroys the winch and accidentally blows up the central cistern
of Iram. Marlowe and Talbot corner Nate and Sully, but the floor gives way, throwing Marlowe into
a sinkhole. Nate attempts to save her, but Marlowe sinks to her death, taking Drake's ring with
her. As Ubar collapses, Nate and Sully fight Talbot, who is shot and falls into the sinkhole. Salim
rescues them as the city is engulfed by the desert sands.
Nate and Sully return to Yemen. Sully returns Nate's wedding ring, which he has secretly kept
safe since Nate and Elena's separation. Elena joins them, and Nate offers her his wedding ring
again. The two embrace, and the three fly home on Sully's new seaplane.