The northern bottle-nose suffered a series of convulsions at 7 p.m. and had been struggling with the effects of being out of the water as it was ferried on a barge toward the Thames Estuary, marine experts said.
Rescuers said the whale was breathing quickly in distress and despite the their best efforts, it died, reports CBS News correspondent Sheila MacVicar. Now scientists want to know what brought the whale to London in the first place.
Swaddled in blankets on the barge, the mammal — watched by thousands in London as it spent two days swimming up the River Thames past some of the capital's most famous landmarks — had shown signs of increasing stress and stiffening muscles, an indicator it was in serious difficulty.
"It was a brave, valiant, but ultimately tragic effort to get the whale to safety," said Leila Sadler, scientific officer at the Royal Society for the Prevention of Cruelty to Animals.
"The animal suffered a series of convulsions at around 7 p.m. and died. It was already dehydrated, hadn't been feeding and the being out of the water would have, in effect, shriveled the animal's internal organs.
"It was essential to try to take the whale out to sea on the barge — but there was always the risk this would happen."
Earlier, the whale was hoisted out of the river by a crane onto the vessel to be sped toward the ocean. Rescue crews were heading toward Margate, on the southern English coast, where they hoped to let the whale back out to sea.
A crowd of 3,000 people at Albert Bridge in south London had cheered and applauded as the whale was tethered to a sling and lifted by a crane onto the "Crossness" barge.
"There was a real chance that the rescue attempt could have succeeded, but these type of mammals are very prone to the effects of stress and I'm afraid it all became too much," said Tony Woodley, spokesman for the British Divers Marine Life Rescue group, who led the rescue attempt.
"It was always going to be a race against time to get it to the ocean, specially with the effect being out of the water has on a whale's body.
"All the crew on the barge are shattered by the death. They were tired and exhausted, but had been determined to do everything they could to get the whale to safety. It really is a terrible shame."
The RSPCA said an international television audience of 23 million had tuned in to news reports across the world Saturday to follow the fate of the whale, the first of its type seen in the Thames since records began in 1913.
Woodley said that a veterinarian will conduct a post mortem examination onboard the salvage vessel to determine exactly why the whale died.
"After that the body will be disposed off, though it is not yet clear how that will be done," he said.