Minister Maurizio Lupi told Parliament he was stepping down even though he is not under investigation. He denies any wrongdoing. No replacement for Lupi was immediately named.
Four people, including the ex-ministry official who oversaw infrastructure projects under seven governments, have been arrested.
Prosecutors are investigating construction contracts involving some of Italy's most ambitious projects, including stretches of a high-speed train line, the Italian pavilion for the world's fair that opens soon in Milan and Rome's subway expansion.
There will be "no consequence of a political nature for the government," Renzi told reporters in Brussels. "We will go forward with reforms."
With fighting corruption one of Renzi's priorities, some in the government sought to put a positive spin on the resignation of Lupi, who is from the New Center Right party founded by defectors from former Premier Silvio Berlusconi's center-right party.
"I think that this government can come out strong from this chapter," Agriculture Minister Maurizio Martina was quoted as saying by the Italian news agency ANSA.
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