Santos pleaded not guilty later Wednesday afternoon during a 10-minute arraignment and was released on $500,000 bond after surrendering his passport.
He left the courthouse to a crowd of cameras and reporters and defiantly said he will not resign.
"This is the beginning of the ability for me to address and defend myself," Santos told reporters afterward, vowing to clear his name and calling his prosecution a "witch hunt."
Santos said he will plan to return to Washington on Thursday and said he appreciates that House Republican leadership is "being patient" with him and the legal process.
"We have an indictment, we have the information that the government wants to come after me on and I'm going to comply," Santos said. "I've been complying throughout this entire process."
Eyewitness News Reporter Sonia Rincon got reaction from officials and New Yorkers on the federal charges brought against Santos.
Constituents call for Rep. Santos to resign after federal charges
Santos will be confined to New York, Washington, D.C., and places in between but he may travel to other places with advance approval.
Santos will not wear and ankle monitor.
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He is charged with seven counts of wire fraud, three counts of money laundering, one count of theft of public funds, and two counts of making materially false statements to the House of Representatives.
The indictment was returned on Tuesday under seal by a federal grand jury sitting in Central Islip.
The indictment says Santos induced supporters to donate to a company under the false pretense that the money would be used to support his campaign. Instead, it says, he used it for personal expenses, including luxury designer clothes and to pay off his credit cards.
Santos also is accused of lying about his finances on congressional disclosure forms and applying for and receiving unemployment benefits while he was employed as regional director of an investment firm and running for Congress.
U.S. Attorney Breon Peace said the indictment "seeks to hold Santos accountable for various alleged fraudulent schemes and brazen misrepresentations."
"Taken together, the allegations in the indictment charge Santos with relying on repeated dishonesty and deception to ascend to the halls of Congress and enrich himself," Peace said.
Santos was arraigned later Wednesday afternoon before U.S. Magistrate Judge Arlene R. Lindsay at the federal courthouse.
RELATED | George Santos indictment outlines 3 main fraud schemes
Despite House Republican leaders appearing to stand by Santos, New York Gov. Kathy Hochul encouraged the congressman to resign.
"I did call for George Santos to resign when these incredible information was starting to come out, I think its important that justice be done, that he deal with the consequences and we will let the courts play it out," Hochul said. "His constituents deserve a lot better than that, they deserve someone that is full time, representing them, an honest individual, people want honestly in their elected officials. And also, we will see what happens. These are charges, we will see what comes, if there is a conviction, obviously there is an automatic removal from office. In the meantime, he continues, I think he should just do the right thing and put this district out of its misery and move on."
Rep. Ritchie Torres issued a statement saying the criminal prosecution of Santos is "long overdue."
"He is a pathological liar and lawbreaker who lied to the voters of New York State and defrauded his way into the United States Congress," the statement read. "About 800,000 Americans have been continually deprived of the honest representation they deserve in the People's House. Although the details of the federal prosecution are not yet fully known, one thing is crystal clear - either Rep. Santos must resign or House Republican leadership, under Speaker Kevin McCarthy, must summon the courage to join House Democrats in expelling him. Rep. Santos is a deep rot of corruption at the core of Congress."
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These charges come just a month after the embattled congressman announced he would run for re-election.
On Tuesday night, Santos' political opponents demanded he resign from congress.
Robert Zimmerman was the Democrat who ran against Santos and tried to spread the word about Santos' many lies. Zimmerman called on House Speaker Kevin McCarthy to dump Santos from his conference.
Nassau County Legislator Josh Lafazan condemned Santos for having the nerve to run again in light of misleading voters the first time.
"To think that one human being would have the audacity to vote for you after what you did to our constituents, then you're either insane, incompetent or a little bit of both," Lafazan said.
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Santos was elected to Congress last fall after a campaign built partly on falsehoods. He told people he was a wealthy Wall Street dealmaker with a substantial real estate portfolio who had been a star volleyball player in college, among other things. In reality, he didn't work at the big financial firms he claimed had employed him, didn't go to college and had struggled financially before his run for public office.
Questions about his finances also surfaced. In regulatory filings, Santos said he loaned his campaign and related political action committees more than $750,000, but it was unclear how he would have come into that kind of wealth so quickly after years in which he struggled to pay his rent and faced multiple eviction proceedings.
In a financial disclosure form, Santos reported making $750,000 a year from a family company, the Devolder Organization, but the charges unsealed Wednesday allege that Santos never received that sum, nor the $1 million and $5 million in dividends he listed as coming from the firm.
Santos has described the Devolder Organization as a broker for sales of luxury items like yachts and aircraft. The business was incorporated in Florida shortly after Santos stopped working as a salesman for a company accused by federal authorities of operating an illegal Ponzi scheme.
ALSO READ | The saga of Rep. George Santos: Inside his many fabrications, exaggerations, and embellishments
The congressman's constituents have expressed outrage at the lies Santos fabricated while campaigning and have held protests outside of his Long Island office.
This indictment may not be the end of his legal troubles because several agencies in New York are investigating him, including the New York Attorney General as well as district attorneys in both Queens and Nassau County.
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Some information from the Associated Press and ABC News
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