The episode starts with Vincent Van Gogh screaming and people looking at his new painting but you don't see what the picture is of until later. We travel to the Second World War where Winston Churchill has seen the picture. Finally, we travel roughly 3000 years into the future from now. River Song is in prison which she breaks out of by mind controlling her prisoner by kissing him. river tries to steal some ornaments from the Royal Collection in the future but is caught by Queen Liz 10.
The Doctor and Amy Pond arrive on a planet where The Doctor is hoping to decrypt a message written on a wall which no one has been able to understand. When the Tardis arrives, we see that the message on the wall is "Hello Sweetie" which is River Song's catchphrase.
The Doctor and Amy travel back in time to 102 A.D., the time when Romans had invaded the British Isles. The Doctor arrives at Stonehenge where there is a large Roman battalion stationed nearby. The Doctor meets up with River Song who is disguised as Cleopatra, the famed Egyptian princess. River tells him that the Pandorica is stationed nearby and they go off to find it. The Doctor discovers an underground chamber and travels down into the catacombs.
In the underground chamber, the Doctor finds an old Cyberman helment which he ignores as he believes it to be harmless and breaks into a chamber behind a locked door, Inside the room is a chamber with a large cube inside the middle. The Doctor tells Amy that the Pandorica is a prison that was designed to hold a dragon that was hell bent on destroying the universe and was imprisoned there by a powerful wizard. Amy remarks that the Pandorica is similar to Pandora's Box, a mythical box holding evil in the world before it was opened. Whilst the Doctor and Amy are investigating the chamber, River Song is piloting or trying to pilot the Tardis.
The Doctor comes under attack from Cyberman's arm which is firing at them. Amy is used as a decoy so that the Doctor can deactivate the Cyberman's arm. However, it is not long before the rest Cyberman comes to life and fires at the Doctor. The Doctor and Amy run into a room to hide from the Cyberman which keeps firing but is disabled when he is speared with a sword from a Roman.
When the Doctor leaves the safe room, he is greeted by Rory Williams who had previously disappeared in the Crack in the Universe. Rory is now a Roman centurion. Whilst the Doctor recognises Rory, Amy does not which upsets Rory.
River Song arrives in 2010 in the Tardis and looks into Amy's house. When River goes into Amy's bedroom she find things that relate to where the Doctor is now. There is a book on Pandora's Box and a picture of Rory as a Roman Centurion. The Doctor tells River to get out of there as he realises what is going on.
The Doctor discovers that there is a large number of spaceships in orbit around the planet and goes outside. The Doctor delivers a speech warning the spaceships to stay away which seems to work as the spaceships leave. On hearing the Pandorica is opening, the Doctor runs down to the chamber. When the Pandorica open, three coloured Daleks appear. The Pandorica is opened for the Doctor to take his place in the seat. The Daleks have formed an alliance with the Cybermen, Judoon and the Sontarans to name a few.
Outside Rory reveals himself to be an Auton, a plastic robot but with all the memories and interests as Rory. Amy starts to remember Rory with Rory trying to keep his Auton side in control. In the end, Rory shoots and kills Amy Pond.
The Doctor is put in the seat and the Pandorica is closed. Explosions start going on around the Earth in space and lights start to go out.
The be continued in The Big Bang.