The whale, which was about 26-years-old, died Friday after suddenly contracting pneumonia in the Taknes fjord in Norway.
Caretaker Dane Richards told The Associated Press that the illness struck the 25-foot mammal fairly quickly as Keiko appeared lethargic and lost his appetite.
"We checked his respiration rate and it was a little irregular ... he wasn't doing too well," Richards said. "Early in the evening, he passed away."
In the wild, orcas can live an average of 35 years. Keiko was believed born in 1977 or 1978 off Iceland.
The drive to free Keiko, who was captured near Iceland in 1979 and sold to the marine park industry, began in 1993 after he was found ailing in a Mexico City aquarium. He was rehabilitated at the Oregon Coast Aquarium, then airlifted to Iceland in 1998.
His handlers prepared him for the wild, teaching him to catch live fish in an operation that cost about $500,000 a month. That same amount paid for a year of care in Norway, according to the Free Willy Foundation in San Francisco.
Keiko, which means "Lucky One" in Japanese, was released from Iceland in July 2002 with hopes that he would return to the wild. But he swam straight for Norway on an 870-mile trek that seemed to be a search for human companionship.
The 6-ton whale delighted Norwegians when he first turned up near the village of Halsa in late August or early September of 2002. He allowed fans to pet and play with him, even crawl on his back, becoming such an attraction that animal protection authorities imposed a ban on approaching him.
But his choice of Norway, the only country that hunts whales for profit, was a shock to many fans, who feared that whalers would go after him. Orcas are protected in Norway, which only hunts minke whales, and authorities assured the world he was safe.
Lars Olav Lilleboe, of the township of Halsa, said it was a sad day for the town of 1,750 people, a mix of rolling farmland and small mountains, some 250 miles northwest of the capital, Oslo.
"He is one of the biggest things to ever happen to Halsa," said Lilleboe. "There is no doubt that he has been a tourist attraction."
Nick Braden, a spokesman of the Humane Society of the United States, said veterinarians gave Keiko antibiotics after he showed signs of lethargy, but it wasn't apparent how sick he was.
"They really do die quickly and there was nothing we could do," he said.
Braden said "it's a really sad moment for us, but we do believe we gave him a chance to be in the wild."
David Phillips, executive director of the San Francisco-based Free Willy-Keiko Foundation, said Keiko's plight changed public perception of whether a whale could be returned to the wild.
"We took the hardest candidate and took him from near death in Mexico to swimming with wild whales in Norway," he said. "Keiko proved a lot of naysayers wrong and that this can work and that is a very powerful thing."
Back in Oregon, where he had spent 32-months at the Coast Aquarium, more than 2.5 million people visited him.
Mark Collson, an aquarium board member, said Keiko had a way with people.
"I once I had a friend describe him as a 4,000-pound golden retriever," Collson said. "He was like the family dog; he wanted to be next to you."
In the end, Phillips said, Keiko's lure is likely to prove beneficial because "there was something about Keiko that wherever he went - Mexico, Oregon, Iceland - he captured the world's attention."
Phillips said that caretakers would have to make burial arrangements with Norway's government.
"My preference would be to bury him on land ... If you bury him on land we could still recover his skeleton and that might have some value in a museum or something, but that is still being worked out," he said.
Meanwhile, Keiko's remains were covered with a tarp in the water of Taknes Bay, a clear, calm pocket of coastal water deep enough that it doesn't freeze in winter. Keepers had fed him there, but he was free to roam, and often did at night.
He was equipped with a VHF tracking device that let his four handlers pinpoint his location provided he stayed within a range of about five miles.
Keiko's stardom came from the three "Free Willy" films, in which a young boy befriends a captive killer whale and persuades him to jump over a sea park wall to freedom.
In November, Keiko was led to his new home at Taknes Bay, still in Halsa but, handlers hoped, farther from the crowds.