Speaking on 2KY's Big Sports Breakfast on Tuesday, Clarke said: "It's a concern for us, a concern for cricket and we can't afford that (split). Cricket in general can't afford it," he said.
"I think it will be the end of cricket if that ever happens and I really hope that isn't the case," the Daily Telegraph quoted him, as saying.
Champions League: BCCI and ECB part ways
Clarke's comments come as ICC seeks to convince the cricket boards of Australia, England, New Zealand and South Africa of the need to hold this year"s Champions Trophy in strife-torn Pakistan.
Security fears have the Aussies and Kiwis, along with England and South Africa, prepared to boycott the one-day tournament.
Then there is ongoing tension between England and India over the staging of their respective Champions League tournaments later in the year.
Even though a split seems highly unlikely, Clarke shuddered at the thought.
Former Australian captain Steve Waugh stressed the need for the world's cricketing nations to pull in the same direction.
"I think they have to work at that relationship because there's definitely the potential there for something like that (a split) to happen," Waugh said.
Cricket Australia's general manager of public affairs Peter Young said: "We're certainly not thinking about any splits and our relationship with the subcontinent is important.
"At the moment there are a number of issues facing world cricket. There are the Twenty20 concepts in England and India, and the issues dealing with Pakistan and the Champions Trophy are frighteningly difficult.
"It's important for world cricket that Pakistan cricket is strong, and the only way they can stay strong is if the likes of Australia visit there regularly.
"Pakistan have said they want us there, we've made it clear we want to come, but it has to be safe."