Smaghi, who has an economics doctorate from the University of Chicago, ends his term at the ECB on 31 May 2013 but said he will instead take up a new role at Harvard University on 1 January 2012.
ECB president Mario Draghi in a statement thanked Smaghi for his “contributions in the field of European and international monetary and economic affairs over many years”.
Smaghi’s resignation clears the way for France to appoint one of its preferred candidates to the ECB’s board and ends a period of friction with president Nicolas Sarkozy over the bank’s six executive members.
Tensions have run high since Draghi, another Italian, was elected president of the ECB, giving Italy two seats while France has no representative since the exit of outgoing ECB president Jean-Claude Trichet.
Italian prime minister Silvio Berlusconi was forced to call for Smaghi to step down in recent weeks as Sarkozy became increasingly impatient after Draghi stepped up to replace Trichet.
France may now propose a candidate of its own, though Smaghi’s successor is not obliged to be French.