Commissioner Margrethe Vestager said: «Banks have to respect EU competition rules just like any other company operating in the single market.»
The Commission fined JPMorgan Chase €337m, Credit Agricole €115m, and HSBC €34m.
It said the banks were part of a cartel relating to products used to manage the uncertainty of interest rate movements.
The investigation found that the cartel operated between September 2005 and May 2008.
Traders used chat rooms and instant messaging to tell each other desired or intended Euribor positions.
This distorted the pricing of financial products based on Euribor, the Commission said.
A JP Morgan spokeswoman said the banking giant had done nothing wrong.
«We have cooperated fully with the European Commission throughout its five year investigation,» she said.
«We did not engage in any wrongdoing with respect to the Euribor benchmark. We will continue to vigorously defend our position against these allegations, including through possible appeals to the European courts.»
An HSBC spokesman said: «We believe we did not participate in an anti-competitive cartel. We are reviewing the European Commission’s decision and considering our legal options.»
In 2013 the European Commission fined eight banks €1.7bn for euro and yen interest rate-rigging.
Two of the eight, whistleblowers Barclays and UBS, were excused their financial penalties.