He pledged to draft a list of firms whose failure would put the U.S. economy at risk in his first 100 days in office and require those firms to reorganize within a year, saying that "if a bank is too big to fail, it is too big to exist."
The Vermont senator and Democratic presidential contender repeatedly cast rival Hillary Clinton as too close to moneyed interests to seriously take on the banks that have faced $204 billion in fines since 2009.
It was an in-your-face approach -- with Sanders coming to Manhattan to condemn those in the nation's financial center -- designed to elevate an issue that Sanders sees as a winner with the first votes in Iowa and New Hampshire just a month away.
"The reality is that fraud is the business model on Wall Street," he said. "It is not the exception to the rule. It is the rule."
He issued a rebuttal of Gordon Gekko, the main antagonist of Oliver Stone's 1987 film "Wall Street," who famously remarked that "greed is good."
"To those on Wall Street who may be listening today, let me be very clear: Greed is not good," Sanders said.
"In fact, the greed of Wall Street and corporate America is destroying the very fabric of our nation. And here is a New Year's resolution that I will keep if elected president -- and that is if Wall Street does not end its greed, we will end it for them," he said.
Sanders also called for the reimplementation of the Depression-era Glass-Steagall Act, which separated commercial and investment banks until it was repealed under President Bill Clinton. It's a major split in the Democratic primary, as Clinton argues that putting that divide back in place would do little to prevent the excesses that caused the 2008 economic tumble.
Sanders took several shots at Clinton, saying that "Secretary Clinton is wrong" and characterizing her as part of a political establishment that he said is to blame for income inequality.
"My opponent says that, as a senator, she told bankers to 'cut it out' and end their destructive behavior. But in my view, establishment politicians are the ones who need to cut it out," Sanders said.
"The reality is that Congress doesn't regulate Wall Street. Wall Street, its lobbyists and their billions of dollars regulate Congress," he said.
Sanders also attacked the financial sector more broadly. He proposed turning for-profit credit agencies into non-profits, and called for caps on ATM fees of $2.
And he pledged to lock those who have worked for major financial firms out of jobs in his administration if he's elected.
"Goldman Sachs and other Wall Street banks will not be represented in my administration," Sanders said.
For Sanders, it's a political posture that has resonated with much of the Democratic base, but he still faces serious obstacles in his bid to undercut Clinton on economic reform.
Just before Sanders' speech, New York City Mayor Bill de Blasio -- another icon of the left -- endorsed Clinton's Wall Street policy platform.
And in a pre-buttal to Sanders' speech, Clinton chief financial officer Gary Gensler, the former head of the Commodity Futures Trading Commission, prodded Sanders to endorse Clinton's Wall Street plan.
"Senator Sanders should go beyond his existing plans for reforming Wall Street and endorse Hillary Clinton's tough, comprehensive proposals to rein in risky behavior within the shadow banking sector," Gensler said.