The Orca was actually involved in the deaths of three people: also killing a man trespassing on SeaWorld Orlando's property, and a trainer at SeaWorld.
Tilikum had been experiencing declining health and receiving treatment for a persistent bacterial lung infection, the company said.
Tilikum became a household name in 2010 when he killed SeaWorld trainer Dawn Brancheau during a performance.
California cracked down on killer whale breeding and entertainment shows in the last two years, going even as far as the governor signing legislation requiring SeaWorld to end breeding orcas in captivity.
As has been documented by "Blackfish" and Outside magazine, Tilikum was captured from the wild off the coast of Iceland in 1983, when he was approximately 2 years old.
The orca featured prominently in the 2013 documentary "Blackfish" which focused on his capture from the wild and what the filmmakers posited as the trauma he suffered from living in captivity and performing in SeaWorld's theatrical shows. In 1991, he was transferred to SeaWorld Orlando and was there for 25 years.
"Blackfish" led to a sharp decline in SeaWorld attendance, leaving the company's leaders to try different approaches to overcome the fallout the documentary caused. Outside SeaWorld parks, the animals could "spend the rest of their lives in as natural a setting as possible, which, contrary to the company's greedy claims, is both reasonable and achievable", PETA Senior Vice President Lisa Lange said in a statement.
The black-and-white five-tonne bull orca, the largest killer whale in captivity, had been linked to the deaths of three people.
While at Sealand in 1992, Tilikum and two female orcas were responsible for the death of a part-time trainer who slipped and fell into their pool and was submerged by them.
Tilikum, possibly the most famous orca in the world, has died, according to SeaWorld Orlando.
Daniel Dukes, 27, hid in the park after closing and evaded security before climbing naked into the killer whale tank.
In the film, former trainers at SeaWorld criticized the park's practices as harmful for orcas and unsafe for trainers.
In that sense, Tilikum's tragic legacy has transformed into something more positive.
"We needed to move where society was moving", Manby said. Stafford said the loss of staff who cared for captive marine mammals may inadvertently weaken other conservation efforts, such as a captive breeding program proposed for endangered porpoises called vaquitas in the waters off Mexico. He must be the last orca to die at a SeaWorld abusement park.
"That human experience isn't likely to be replaced", Stafford said.