The centre-left candidate, Fabrizio Micari, came third on just under 19 per cent.
The result marked a triumphant comeback for centre-right Forza Italia (FI) leader Silvio Berlusconi.
The former premier campaigned heavily for Mr Musumeci leading up to the vote, promising Sicilians everything from a bridge over the Messina Strait to a casino in Taormina.
“Sicily has chosen - as I asked - the road of change. Of a real, serious and constructive change based on honesty, competence and experience,” Mr Berlusconi wrote on his Facebook page.
“I have met many Sicilian voters over the past few days and I found anger and disappointment, but also a desire to start again.”
Mr Berlusconi, whose FI ran with the anti-immigrant, anti-euro Northern League (LN) and the small nationalist Brothers of Italy (FdI), saw the win as a gateway to victory in next year’s general election.
However, less than half of those eligible to vote took to the polls during Sicily’s election.
Some have contended that the low voter turnout minimises the regional election’s status as an indicator for the national election, due by March 2018.
The turnout was 46.76 per cent, meaning 2,179,474 of 4,661,111 people with the right to vote on the southern island did so between 8:00 am and 10:00 pm on Sunday.