The double amputee sprinter, once revered across the world for his triumph over physical adversity, faces life in prison if convicted of the murder of Reeva Steenkamp, a 29-year-old law graduate and model.
Pistorius, known as "Blade Runner" due to the prosthetics he wears on the track, says he shot Ms Steenkamp in a tragic accident, firing at what he thought was an intruder hiding behind a toilet door in his luxury Pretoria home on February 14 last year.
Prosecutor Gerrie Nel, whose reputation as one of South Africa's toughest attorneys has earned him the nickname "The Pitbull", cross-examined Pistorius at Pretoria High Court while looking through photographs of the couple's bedroom taken after the shooting.
In a period of fierce questioning, Nel pointed out a series of objects in one picture that ran counter to Pistorius's account of events. In response, the sprinter accused the police of tampering with the scene, but Mr Nel ridiculed this suggestion.
"Let's sum up: A policeman moved the two fans, put the duvet on the floor, opened the curtains wider than they should be before the photographs were taken," Mr Nel said.
"Your version is so improbable that nobody would ever think it's reasonably possibly true ... your version is a lie."
Pistorius says that after he shot Ms Steenkamp, he ran out on to the balcony and screamed for help. However, in a picture shown to the court, a duvet and a large stand-up electrical fan block his route to the balcony door.
With no direct witnesses, Mr Nel's main task is to challenge Pistorius's testimony and cast doubt on his assertion he believed a burglar was in his house, a common fear in crime-ridden South Africa.
Witnesses in nearby buildings have testified to hearing a woman's scream before the sound of shots, which the prosecution hopes will help prove the couple had a heated argument before Pistorius intentionally killed Ms Steenkamp.
During much of the 19-day trial, Mr Nel has sought to portray Pistorius as an arrogant hot-head who is reckless with firearms and refuses to take responsibility for his actions.
"You will blame anybody but yourself," he said to the 27-year-old athlete, cross-examining him about a separate incident in which he is accused of firing a pistol in a packed restaurant.
Pistorius said the gun was given to him by a friend under the restaurant table and went off by itself. Police Captain Christian Mangena gave evidence earlier in the trial, saying the weapon could only fire if the trigger was pulled.
The athlete said he could not explain how the gun went off and questioned his own defence advocate Barry Roux's decision not to cross-examine Mr Mangena on his evidence.
"Now you blame counsel Mr Roux," Mr Nel said, prompting Mr Roux to shake his head at a colleague.
"You are lying," Mr Nel said, staring at Pistorius. "You just refuse to take responsibility for anything."
In a dramatic opening to his cross-examination on Wednesday, Mr Nel shocked the Pretoria court when he confronted Pistorius with a graphic photograph of the dead Ms Steenkamp showing the side and back of her skull, her hair matted with blood and brain tissue.
Pistorius sobbed as Mr Nel pushed him repeatedly to take responsibility for the killing.
The trial continues.