The Italian bank has put chairman Dieter Rampl into his position on an interim basis as it begins the search for a replacement.
Mr Profumo left the financial institution following arguments with Italian shareholders over increased investment from Libyan organizations, reports Bloomberg.
The Central Bank of Libya holds a five per cent stake in UniCredit and the Libyan Investment Authority recently increased its stake in the bank from 0.5 per cent to 2.6 per cent.
Insider sources said Mr Profumo was asked to resign by some of the largest Italian shareholders because he did not inform them Libyan investors were intending to raise their stakes in the business.
Earlier this year, UniCredit sold off discounted shares in a bid to raise â¬4 billion ($5.8 billion) and strengthen the state of its balance sheet after being hit hard by the effects of the global financial crisis.
By Claire Archer