Unemployment in Puerto Rico, which has a population of nearly four million, was 15.8 per cent in August, higher than any US state.
The Caribbean island, which is home to several petrochemical, pharmaceutical and technology companies, has been in recession for more than three years.
Police guarded government buildings in San Juan as protesters headed to the Hato Rey financial district near Plaza Las Americas, the Caribbean's largest mall.
The mall, with 300 stores and more than 10,000 employees, shut its doors, along with other businesses and private schools in the area.
Some traffic routes were blocked by protesters in early morning protests and many streets were empty as people decided to stay at home for the duration of the strike.
Fortuno has said that the job cuts will prevent the country's bond rating from being downgraded to non-investment grade and that the firings will lead to a cut in government spending by $2bn a year.
He has argued that a credit downgrade would cause more harm to the economy and lead to job cuts far in excess of those made in the public sector.
The government has passed a series of spending cuts and recruitment freezes, and has imposed temporary taxes.
It has also sunk money into public infrastructure investment and low-cost financing to help boost the economy, which shrank a record 5.5 per cent in the 2009 fiscal year that ended June 30.