The Court of Cassation rejected appeals to overturn his acquittal on charges of underage sex with a prostitute and abusing his office to cover it up.
Berlusconi, 78, hailed the ruling as a beautiful day for politics, justice and the rule of law.
“I am back in the field with Forza Italia,” he said.
The three-time Italian prime minister remains embroiled in several legal battles and is barred from running for election under the Severino law, which bars from office anyone sentenced to more than two years in jail.
But his supporters aim to overturn the 2012 legislation.
‘Finally, the truth’
Berlusconi was initially given a seven-year jail term in 2013 in what became known as the “bunga bunga” case, before having the verdict overturned on appeal last July.
He and the 17-year-old dancer involved, Karima El-Mahroug, known as “Ruby the Heartstealer”, had denied having had sex.
Last week, he completed a community service order with elderly dementia patients as part of a separate conviction for tax fraud.
Supported by Forza Italia colleagues, Berlusconi said on Wednesday that the path was now clear for a return to mainstream politics.
“Finally, the truth,” he said, describing the court case as a sad page he was leaving behind.
“I was certain that my reasons would be understood. However, what remains is the regret of an issue that has caused severe damage not only to me but to all Italians.”
He remains under investigation for allegedly paying off witnesses in the “bunga bunga” case, and is on trial in Naples for alleged political corruption.