Washington would consider the establishment of such a zone - which would require civilian aircraft to identify themselves to military controllers - "a provocative and destabilising act," Kerry told reporters in Ulan Bator.
The remarks came on the eve of a US-China dialogue in Beijing and after a Hong Kong newspaper cited Chinese army sources as saying Beijing was mulling such a zone, similar to one Beijing established over the East China Sea in 2013.
Washington has responded by sending warships close to Chinese claimed reefs, angering Beijing.
Further US actions in the region "will give Beijing a good opportunity to declare an ADIZ in the South China Sea," a Chinese army source told the South China Morning Post newspaper last week.
Kerry said such a move would "raise tensions".
"We would consider an ADIZ, an ADIZ zone, over portions of the South China Sea as a provocative and destabilising act, which would automatically raise tensions and call into serious question China's commitment to diplomatically manage the territorial disputes of the South China Sea," Kerry said.
Kerry also repeated Washington's standard line that it does not take sides in disputes over the sea.
But that stance has been called into question by US Defense Secretary Ashton Carter, who last month accused Beijing of "pressing excessive maritime claims contrary to international law".
China blasted his remarks as expressing "typical US thinking and US hegemony" and a "cold war mentality".
Carter warned a regional security forum in Singapore yesterday that Chinese construction on an islet claimed by the Philippines would prompt "actions being taken" by the US and other nations.