The 69-year-old said "tax breaks to millionaires and billionaires who don't need it" were unconscionable and worsen the national debt.
He spoke for long periods in an otherwise empty Senate chamber. He was briefly spelled by Sen. Mary Landrieu, D-La., who also opposes the bill.
Lawmakers still expect the Senate to approve the bill next week and send it to the House.
Officially an independent, Sanders is one of the most liberal senators and typically sides with Democrats.
As he wrapped up his speech after nightfall, Sanders conceded, "It has been a long day."
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