It is 5:02 PM on April 22nd, 2011, the day the Doctor dies at Lake Silencio. In London something has gone wrong with history. Various historical eras have collided into one another with Pteranadons and balloon borne cars flying through the London skies and Roman chariots making their way through traffic. On TV Charles Dickens is interviewed about his latest Christmas Special while a newsreader announces that Holy Roman Emperor Winston Churchill has returned to Buckingham Senate on his personal mammoth. In his office, Churchill is examined by his Silurian physician and wonders why it is always the exact same time. He has an imprisoned soothsayer brought before him who turns out to be the Doctor.
The Doctor explains how in the last days before his trip to Lake Silencio he traveled through time trying to discover why the Silence want him dead and how he might stop them. He meets with the crew of the Justice Department Tesselecta and then forces an alien viking to take him to the preserved head of Dorium Maldovar. Dorium explains that the Silence want the Doctor dead to prevent him from fulfilling a prophecy regarding the oldest question in the universe, the asking of which will cause their fall.
At first determined to outrun his own death, The Doctor changes his mind after learning of the death of his former companion Brigadier Lethbridge-Stewart, which causes him to realize that everyone must die eventually. Traveling to Lake Silencio he confronts River in the space suit. River explains that she's not in control but the Doctor forgives her and explains that he has made peace with his death and that it is a fixed point in time.
However, River refuses to kill the Doctor, discharging her weapon harmlessly. This violation of a fixed point in time causes time itself to unravel, with all of history happening at once. In London the Doctor realizes that the Silence are menacing him and Winston Churchill, but he is rescued by Amy Pond who is leading a paramilitary team.
Amy, who, like all her team, is wearing an eye patch similar to that of Madam Kovarian, takes the Doctor aboard a private train headed to Cairo. She reveals that she remembers the Doctor and most of her adventures, although she cannot remember her husband Rory, who is in her service as Captain Williams. The Doctor explains that he has to die in order to put history right, otherwise all of existence will unravel.
Arriving in Cairo they head to Area 52 inside the Great Pyramid of Giza. There, Amy's team has captured and imprisoned hundreds of Silence as they try to discover what has gone wrong with time. They explain that the patches are really "eyedrives" which allow them to remember the Silence when they are not looking at them.
They lead the Doctor to a room where River has imprisoned Madam Kovarian. Upon meeting River, the Doctor grabs her, their physical contact causing time to begin to move again as the history of the Doctor's death begins to play out. However, River breaks the contact, unwilling to murder her beloved.
Meanwhile, Madam Kovarian reveals that the Silence had allowed themselves to be imprisoned and the aliens break out of their containment tanks. They attack the humans by causing their eyedrives to electrocute them. As the Doctor and River flee to the top of the pyramid, Amy rescues Rory from the Silence, finally realizing that he is her husband. She then resets Madam Kovarian's eyedrive in place so that it will electrocute her and leaves the woman to die.
Realizing that he has to gain River Song's trust, the Doctor agrees to an impromptu marriage ceremony and whispers something into her ear. As they kiss, history reverts to its original state with the Doctor apparently getting killed at Lake Silencio.
With history put right, River visits a grieving Amy at home. She then reveals her secret to Amy. The Doctor is not dead. What they saw at Lake Silencio was actually a Tesselecta in the form of the Doctor with him riding inside.
In the finale scene the Doctor replaces Dorium Maldovar's head in its resting place and explains how he intends to "return to the shadows" allowing the universe to think that he is dead. Dorium then reveals that the question which so frightens the Silence is "Doctor who?"