About five minutes into trade, the Dow Jones Industrial Average stood at 17,500.74, down 510 points, or 2.8 per cent.
The broad-based S&P 500 fell 2.7 per cent to 2,055.42, while the tech-rich Nasdaq Composite Index dropped 3.5 per cent to 4,737.79.
Analysts described the US investor reaction to the unexpected outcome in Britain as negative and decisive, yet relatively orderly.
"All that can be determined at this juncture is that there is a heightened feeling of uncertainty following the UK vote and a heightened sense of dismay that, for the first time since the financial crisis, a purported 'worst-case scenario' has actually happened," said Briefing.com analyst Patrick O'Hare.
"The extreme reactions to the vote speak to the equally high level of complacency in the thought that a worst-case scenario would not happen."
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