Brussels in May gave the takeover a green light, just weeks after Britain's Competition and Markets Authority (CMA) blocked it, arguing it would harm competition in cloud gaming.
The split is the most significant between E.U. and U.K. regulators since Brexit.
Vestager, the European Commission vice president, told reporters in Brussels that the E.U. was satisfied with the commitments made by Microsoft that it would not make games "exclusive" to its own cloud gaming service.
"Where we diverged with the CMA was on remedies. We accepted a 10-year free license to consumers to allow them to stream all Activision games for which they have a license via any cloud service," Vestager said.
"And why did we do this instead of blocking the merger? Well, to us, this solution fully addressed our concerns. And on top of that, it had significant pro-competitive effects," she argued.
But Vestager noted the "divergence raises important questions regarding our assessment, our remedies policy and our cooperation."
Microsoft filed an appeal against the CMA's decision with the U.K. Competition Appeals Tribunal on May 24, a company spokesman told AFP.
Microsoft's bid is also under threat in the United States as well where the Federal Trade Commission (FTC) launched a legal action to block it last year, one of Washington's biggest ever interventions to stop tech industry consolidation.
It could be game over for the merger unless Microsoft successfully fights off the challenges in Britain and the United States.