The bank is accused of coordinating with traders at other banks to make false reports related to setting key global interest rates. The rates affect the costs of hundreds of trillions of dollars in loans and investments.
The U.S. Commodity Futures Trading Commission said the incidents happened between 2005 and 2009, and Barclays senior management and several traders were involved.
The data was used in determining the London interbank offered rate - known as LIBOR- and Euribor rates, which influence many other interest rates.
"Banks must not attempt to influence LIBOR or other indices based upon concerns about their reputation or the profitability of their trading positions," CFTC Chairman Gary Gensler said in a statement.
Barclays' settlement includes a $200 million civil penalty. Britain's Financial Services authority levied a fine of 59.5 million pounds ($92.7 million), the biggest fine ever imposed by the British regulator. Barclays also agreed to pay $160 million as part of an agreement with the fraud section of the Justice Department's criminal unit on a related matter.
The Associated Press contributed to this report.