Investors also were uncertain how much farther China will go with a regulatory crackdown that set off a slide in its internet share prices.
Shanghai, Tokyo and Sydney retreated while Hong Kong advanced.
Investors were digesting U.S. earnings reports while worries increased after the Centers for Disease Control and Prevention recommended even vaccinated people return to wearing masks indoors in areas where the coronavirus's more contagious delta variant is spreading.
“Investors turned cautious,” said Edward Moya of Oanda in a report.
A meeting of the Federal Reserve board that began Tuesday is expected to bring an update on when the U.S. central bank might start to reduce bond purchases that inject money into financial markets and keep interest rates low.
The Shanghai Composite Index lost 0.7% to 3,357.28, declining for a third day, while the Nikkei 225 in Tokyo fell 1.4% to 27,581.66. The Hang Seng in Hong Kong gained 1.1% to 25,360.77.
The Kospi in Seoul lost 0.1% to 3,236.86, while Sydney's S&P-ASX 200 gave up 0.7% to 7,379.30.
India's Sensex opened down 0.9% at 52,087.70. New Zealand gained while Southeast Asian markets declined.
On Wall Street the benchmark S&P 500 fell 0.5% to 4,401.46, snapping a five-day streak of gains. The Dow Jones Industrial Average dropped 0.2% to 35,058.52. The Nasdaq lost 1.2% to 14,660.58.
Selling was most pronounced in technology and communication stocks, and in companies that rely on consumer spending. Traders shifted money into sectors seen as less risky, including utilities, health care and in companies that make household and personal goods.
Shares in Chinese internet giants slid for a third day as investors waited for possible new action after Beijing stepped up anti-monopoly and data security enforcement against the industry. They were reported to be considering restrictions on for-profit education ventures.
Games and social media giant Tencent Holding Ltd. fell 3.5% in Hong Kong. E-commerce giant Alibaba Group shares in Hong Kong were down 0.3% after Wall Street-traded shares lost 3%.
On Wall Street, UPS slumped 7% after its quarterly revenue fell short of forecasts. Tesla fell 2% and industrial conglomerate 3M fell 0.6%, despite reporting solid financial results.
In energy markets, benchmark U.S. crude rose 47 cents to $72.12 per barrel in electronic trading on the New York Mercantile Exchange. Brent crude oil, the basis for international oil prices, advanced 39 cents to $73.91.
The dollar advanced to 109.82 yen from Tuesday's 109.72 yen. The euro rose to $1.1818 from $1.1786.