Some 170 police officers and investigators from the prosecutor's office were searching for six of the bank's premises in and around the city.
The timing of the raid inflicts more pain on Deutsche Bank after a series of setbacks and repeated failures in keeping misconduct in check have pushed the shares to all-time lows.
German authorities suspect that Deutsche Bank employees helped clients set up offshore companies in tax havens to launder hundreds of millions of euros.
The investigation is focused on a Deutsche Bank unit based on the British Virgin Islands, which dealt with more than 900 clients and processed 311 million euros ($354 million) in 2016 alone, according to the prosecutors.
They also said Deutsche Bank employees are alleged to have breached their duties by neglecting to report money laundering suspicions about clients and offshore companies involved in tax evasion schemes.
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Deutsche Bank's Frankfurt offices were searched Thursday as part of a probe linked to the Panama Papers. "In recent years, we have proven that we fully cooperate with the authorities - and we will continue to do so". "The investigation has to do with the Panama Papers case". And the author and reporter Luke Harding has described a "shuffle of money" between the bank's dealings with figures in Russian Federation and its business with Trump.
Paperwork and electronic documents were seized by officials during the raids on the bank's properties.
Scrutiny surrounding Deutsche Bank, one of New York's top real estate lenders, has just intensified. The "Panama Papers" data leak comprised some 11.5 million documents and was leaked to German newspaper Süddeutsche Zeitung by an anonymous source in 2015.
And it's not the first time Deutsche Bank has run into trouble over the flow of dirty money. The bank didn't have a complete picture of the compliance controls in the organization's businesses and regions, she said. More details will be communicated as soon as these become known.
An internal investigation by Danske found that about €200bn (£177bn) of payments were funnelled through its Estonian branch.
A number of banks including Swedish lenders Nordea and Handelsbanken have already been fined by financial regulators for violating money laundering rules as a result of the papers. And in 2017, the bank was fined almost $700 million for allowing money laundering.