"Watch Katie Holmes and Scientology story develop. Something creepy, maybe even evil, about these people," Murdoch said on his Twitter account, @rupertmurdoch.
The fairytale Hollywood couple's split was revealed when Holmes' publicist announced that the actress had filed for divorce after five years of marriage, ending an unexpected love story dogged by tabloid rumors.
A spokesman for Cruise said the "Mission Impossible" star was "deeply saddened" by the news, fueling reports that his wife's announcement had taken him by surprise.
Speculation about why Holmes wanted out has included suggestions she was concerned that Cruise was forcing their six-year-old daughter Suri deeper into the Church of Scientology.
The TMZ celebrity news website has reported that Holmes is seeking sole custody of Suri. Citing unnamed sources, it said she feared "that Tom would drag Suri deep into the church."
"We're told the couple had been arguing over Suri - that she's now of the age where Scientology becomes a significant part of her life," it said.
Murdoch's Scientology comment generated a surge of Twitter traffic, prompting another tweet: "Since Scientology tweet hundreds of attacks. Expect they will increase and get worse and maybe threatening.
"Still stick to my story," he added.
There was no immediate response to a request for comment from the Church of Scientology, or from publicists for Cruise or Holmes.