Microsoft shares rallied 7.2% following upbeat quarterly earnings and sales, including of robust artificial intelligence products.
The Dow Jones Industrial Average (.DJI) fell 228.96 points, or 0.68%, to 33,301.87; and the S&P 500 (.SPX) lost 15.64 points, or 0.38%, at 4,055.99.
The S&P 500 technology index (.SPLRCT) was the sole gainer among the benchmark's 11 major industry sectors, adding 1.7%.
Of the 163 S&P 500 companies that reported first-quarter profit through Wednesday morning, 79.8% topped analysts' expectations, as per Refinitiv IBES data.
It helped push the S&P 500 bank index (.SPXBK) down 1.4% on the day.