In a dramatic trading session, major indices turned negative in the final minutes of trading after previously climbing almost 3 percent.
Investors cited more worries that a slowdown in China could hobble global growth, even after the country's central bank cut interest rates on Tuesday for the second time in two months. The move came after Chinese stocks slumped 8 percent on Tuesday, on top of an 8.5 percent drop on Monday.
"People are still nervous about overseas and what might happen tonight. Nobody wants to sit around and see what happens," said Paul Nolte, portfolio manager at Kingsview Asset Management in Chicago.
Tuesday's drop followed steeper losses on Monday, when the Dow Jones industrial average fell more than 1,000 points at its lows and the S&P 500 recorded its worst day since 2011.
In the past week, the S&P has lost 11 percent.
"Investors are still concerned about exogenous growth and shifting Fed policy, and both of those are still on the table," said Mark Luschini, chief investment strategist at Janney Montgomery Scott in Philadelphia.
The Dow Jones industrial average fell 204.91 points, or 1.29 percent, to end at 15,666.44.
The S&P 500 lost 25.59 points, or 1.35 percent, to finish at 1,867.62 and the Nasdaq Composite dropped 19.76 points, or 0.44 percent, to 4,506.49.
Earlier, the S&P rose as much 2.9 percent, the Dow as much as 2.8 percent and the Nasdaq as much as 3.6 percent.
JPMorgan cut its year-end target for the S&P 500 to 2,150 from 2,250.
All of the 10 major S&P sectors were lower, with the utilities index's 3.2-percent drop leading the decline.
Pepco Holdings Inc fell 16.47 percent after a District of Columbia regulator denied Exelon Corp's $6.8 billion bid for the power utility, possibly delivering a knockout blow to the deal.
Monday's pummeling pushed the S&P 500's valuation down to about 15 times expected earnings, compared to around 17 for much of 2015 and just above a 10-year average of 14.7, according to Thomson Reuters StarMine.
Data on Tuesday showed U.S. consumer confidence increased to a seven-month high in August. New U.S. single-family home sales rebounded in July, adding to evidence of underlying strength in the economy that could allow the Federal Reserve to raise interest rates this year.
Best Buy jumped 12.57 percent after the owner of the biggest U.S. electronics chain reported an unexpected increase in quarterly sales.
Decliners outnumbered rising stocks on the NYSE by 1,721 to 1,384. On the Nasdaq, 1,480 issues fell and 1,379 advanced.
The S&P 500 index showed just one new 52-week high and 47 new lows, while the Nasdaq recorded seven new highs and 125 new lows.
Volume was heavy, with about 10.4 billion shares traded on U.S. exchanges, far above the 7.5 billion average this month, according to BATS Global Markets.