BRUSSELS—Europe’s governments should seize a “very, very rare” opportunity to close loopholes that allow corporations to dodge billions in tax, the region’s top antitrust regulator said Monday, as she warned high-profile investigations by her agency couldn’t alone solve the problem of large-scale corporate tax avoidance.

“All of a sudden in most European countries we have a debate about corporate taxation,” said Margrethe Vestager, the former Danish economy minister who took office as the European Union’s competition commissioner six weeks ago.

The public debate provides “fertile ground for new proposals to change how corporate taxation works in the EU,” Ms. Vestager said. “This is truly new and I think it’s good news.”

The comments, at a briefing with journalists here, come as European governments consider how to clamp down on multinational companies that exploit differences in national rules to pay little or no tax. Policymakers are under pressure to show a recession-weary public that large companies are contributing fairly to crisis-hit public purses and aren’t benefiting from special treatment.

The European Commission, the bloc’s top antitrust authority, has opened a series of investigations in recent months into the tax affairs of four multinational companies--Apple Inc. in Ireland, Amazon.com Inc. and Fiat SpA in Luxembourg and Starbucks Corp. in the Netherlands. Those companies have denied receiving special treatment.

In the wake of those probes, Ireland announced it would phase out a tax loophole known as the double-Irish, while Luxembourg is working on legislation to ensure its approval process for corporate tax rulings is more transparent.

Ms. Vestager said she welcomed such moves by national authorities. “We can do something with competition law but it is important to admit its limitations,” she said.

While the commission can strike down tax deals it considers provide a selective advantage to some companies and not others, it has no broader powers to deter tax avoidance.

The commissioner contrasted the current political climate with her efforts in early 2012, as Denmark’s economy minister, to drive through new EU laws aimed at sharing information on personal bank accounts and a common European tax base for companies. Those efforts made very slow progress until recently, in part because of a requirement that all EU governments agree unanimously on tax issues.

“It was no go, it didn’t move one inch,” she said. “I was told the way things are is the way they’re going to stay, and this is the new black. Forget about it.”

Ms. Vestager also said she wouldn’t allow political pressure to sway her decision on a long-running investigation of Google Inc.’s search practices in Europe. The U.S. search giant has been under investigation in Brussels since late 2010 over allegations it abuses its dominant market position to favor its own specialist search services over those of rivals.

The European Parliament last month passed a resolution calling for a possible breakup of Google, a move its proponents said aimed to put pressure on Ms. Vestager to act swiftly against the U.S. search giant. Several senior U.S. politicians hit back, warning that any aggressive action against U.S. technology companies could endanger trade talks with Europe.

The demands from both sides of the Atlantic “put pressure on me to be as fair as at all possible,” Ms. Vestager said.

“The more people have views on the case, the more important it is to be impeccable,” she said.

Write to Tom Fairless at tom.fairless@wsj.com