US authorities said the bank had stripped messages on financial transfers routed through US banks of information that would show the beneficiaries were businesses and entities that fell under US sanctions.
The fines from the Treasury's Office of Foreign Assets Control (OFAC) and other US federal and local regulators took to $667 million the total the bank has been charged for sanctions violations.
In August the New York state banking watchdog fined Standard Chartered $340 million in the same investigation, saying it hid 60,000 transactions with proscribed Iranian clients worth $250 billion over 10 years.
"Today's settlement is the result of an exhaustive interagency investigation into Standard Chartered Bank's attempts to violate US sanctions programs through the 'stripping' from payment messages of critical information," said OFAC Director Adam Szubin in a statement.
The sanctions avoidance involved mainly the bank's London head office and its branch in Dubai, which masked the details of messages so US authorities would not see the real identity of those sending and receiving the payments.
"As a result, millions of dollars of payments were routed through US banks for or on behalf of sanctioned parties in apparent violation of US sanctions," OFAC said in a statement.
OFAC added that the fine also covered eight apparent violations of US sanctions on druglords.
The $327 million settlement included $132 million from OFAC, $100 million from the Federal Reserve, and $95 million from the Department of Justice and other entities.
It was one of the largest assessments ever by the Federal Reserve, which cited "the alleged unsafe and unsound practices related to information provided to Federal Reserve examiners."
The main payments under question took place between 2001 and 2007, the Treasury said.
US authorities are pushing harder on the banking sector to fall in line with its sanctions especially on Iran in order to raise the economic pressure on Tehran to halt its alleged push to develop nuclear weapons.
But the sanctions pressure also relates to alleged terror groups and drug organizations.
In August the global bank HSBC set a provision of $700 million to cover possible fines related to accusations it concealed more than $16 billion in sensitive transactions with Iran and Mexican drug lords over 2001-2007.
"The United States expects a minimum standard of behavior from all financial institutions that enjoy the benefits of the US financial system. Standard Chartered's conduct was flagrant and unacceptable," said Justice Department Assistant Attorney General Lanny Breuer.