Merkel told Pence and other world leaders, diplomats and defence officials at the Munich Security Conference that "acting together strengthens everyone."
Her address came amid concern about the Trump administration's approach to international affairs and fears that it may 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 transatlantic 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.
Merkel reiterated that Germany is committed to the official NATO goal of putting 2 per cent of gross domestic product into defense spending, Germany currently contributes 1.3 per cent.
"We will do everything we can in order to fulfil 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."
"Europe's defence requires your commitment as much as ours," he said.
Merkel said Europeans couldn't fight Islamic extremist terrorism alone, and "we need the military power of the United States."
She renewed a call for Islamic religious authorities to speak "clear words on the demarcation of peaceful Islam and terrorism in the name of Islam.
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