Merkel told Pence and other world leaders, diplomats and defense officials at the Munich Security Conference that "acting together strengthens everyone."
Her address came amid concerns about the Trump administration's approach to international affairs and fears that the US may soon have little interest in working in multilateral forums.
"Will we be able to continue working well together, or will we all fall back into our individual roles?" Merkel asked.
Pence sought immediately to address concerns raised by President Donald Trump's comments questioning whether NATO was "obsolete."
Pence told the group: "I bring you this assurance: The United States of America strongly supports NATO and will be unwavering in our commitment to our trans-Atlantic alliance."
"Your struggles are our struggles. Your success is our success," Pence said. "And ultimately, we walk into the future together."
Merkel conceded room for improvement in multilateral structures, saying that in many places they are not efficient enough.
German Foreign Minister Sigmar Gabriel expressed skepticism about Pence's pledges, saying that he agreed Europe needed to work with the US on the basis of common values. But in a barely veiled reference to Trump, he said "both countries must define their interests, and our foreign policies should not be driven by ideology."
"Ideologies lead to hostile concepts that might not be able to be overcome," said Gabriel, who is chairman of the Social Democratic Party, Merkel's junior coalition partner. Going ahead, he said Europeans "should hope for the best, but prepare for the worst."
"We will do everything we can in order to fulfill this commitment," she said. "But let me add, however, that I believe while NATO is very much in the European interest, it's also in the American interest -- it's a very strong alliance where we are united together."
Pence added bluntly that the U.S. Expected that all NATO members would meet the 2 percent goal.
"Europe's defense requires your commitment as much as ours," he said.
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