Washington wants the G20 to accommodate President Donald Trump's "America First" plan and his demand for what he describes as a fairer trading system that better reflects U.S. interests.
The Washington Post reports that Mnuchin quickly became the center of attention at the gathering, with many foreign leaders seeking to meet with him.
The gathering Friday and Saturday in the southern German resort town of Baden-Baden will help set the tone for global commerce and finance and will give Mnuchin a chance to clarify what the USA position is.
The world's top economic powers dropped a pledge to oppose trade protectionism amid pushback from the Trump administration, which wants trade to more clearly benefit American companies and workers.
U.S. Treasury Secretary Steven Mnuchin speaks at a news conference during the G20 finance ministers meeting in Baden-Baden, southern Germany, March 17, 2017.
Organisation for Economic Cooperation and Development (OECD) head Angel Gurria pointed to similar developments elsewhere, in a "backlash against globalisation" which is seeing growth and economic reforms stutter as populations grumble over inequality.
Both China and Germany have found themselves in the crosshairs of U.S. criticism over their massive trade surpluses.
G20 countries represent more than 80% of global GDP.
The divisions between the USA and other major powers over trade were on display again Friday, when Trump hosted German Chancellor Angela Merkel at the White House. He also rejected a description of his policies as "isolationist".
The G-20 groups Argentina, Australia, Brazil, Britain, Canada, China, France, Germany, India, Indonesia, Italy, Japan, Mexico, Russia, Saudi Arabia, South Africa, South Korea, Turkey, the United States and the European Union.
German Chancellor Angela Merkel and Chinese President Xi Jinping agreed to work together for free trade and open markets, a German government spokesman said. But there is a "desire to deal with where there is imbalance in certain trade relations". Without mentioning a country by name, he said, "Maybe one or the other important member state needs to get a sense of how global cooperation works".
G20 also walked back on a pledge to support climate change finance, an anticipated outcome after Trump called climate change a "hoax".
Some members like France said they were frustrated by the lack of a rejection of protectionism in the final communique.
Trump's administration on Thursday proposed a 31 percent cut to the Environmental Protection Agency's budget as the White House seeks to eliminate climate change programmes and trim initiatives to protect air and water quality.
"It is essential that we affirm that common principles here so that the process can continue to advance", he told AFP.