The two-day talks in Beijing, called the Strategic and Economic Dialogue, will be an opportunity for the world's two biggest economies to bring down tensions after months of bickering over a host of issues.
US Secretary of State John Kerry and Treasury Secretary Jack Lew chair the US delegation, with Vice Premier Wang Yang and top diplomat Yang Jiechi leading the Chinese side.
President Xi Jinping said Sino-US cooperation was of vital importance to the global community.
He told the opening ceremony: "China-US confrontation, to the two countries and the world, would definitely be a disaster.
"We should mutually respect and treat each other equally, and respect the other's sovereignty and territorial integrity and respect each others choice on the path of development."
Escalating tensions between China and some countries in the South China Sea and with Japan in the East China Sea as well as US charges over hacking and internet spying have provoked ire on both sides of the Pacific in recent months.
In a statement released as the discussions began, President Barack Obama said the US was committed to building a "new model" of relations with China that is defined by cooperation and the constructive management of differences.
Mr Obama said: "The US welcomes the emergence of a stable, peaceful, and prosperous China. We remain determined to ensure that cooperation defines the overall relationship."
Despite deeply interconnected business ties and two-way trade worth more than half a trillion dollars a year, Beijing and Washington have deep differences over everything from human rights to the value of the Chinese currency, the yuan.
Washington has begun to push for China to move to a market-driven exchange rate.