The British billionaire, 86, is accused of passing non-public information to employees, friends and romantic interests to make 'millions of dollars'.
Lewis, who owns 85 per cent of Spurs through ENIC, faces 19 counts, including alleged securities fraud.
In a video posted on Twitter, US attorney Damian Williams said: "My office, the Southern District of New York, has indicted Joe Lewis, the British billionaire for orchestrating a brazen insider trading scheme.
"We allege that for years Joe Lewis abused his access to corporate boardrooms and repeatedly provided inside information to his romantic partners, his personal assistants, his private pilots and his friends.
"Those folks then traded on that inside information and made millions of dollars on the stock market because, thanks to Lewis, those bets were a sure thing.
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"Now, none of this was necessary. Joe Lewis is a wealthy man. But as we allege he used inside information as a way to compensate his employees or shower gifts on his friends and lovers. It is classic corporate corruption.
"It's cheating and it's against the law. That's why Joe Lewis has been indicted and will face justice here in the southern district of New York."
Tottenham refused to comment on the news when approached.
The club told Sky News: "This is a legal matter unconnected with the club and as such we have no comment."
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Meanwhile, Lewis' lawyer David Zornow said: "The government has made an egregious error in judgement in charging Mr Lewis, an 86-year-old man of impeccable integrity and prodigious accomplishment.
"Mr Lewis has come to the US voluntarily to answer these ill-conceived charges and we will defend him vigorously in court."