The US territory's power authority, known as Prepa, said it was working to restore service to almost 3.4 million people within 24 to 36 hours.
Prepa said an excavator operated by a contractor in the southern region of the island caused the blackout.
It is the latest and largest disruption to hit the island's recovery efforts.
A Prepa spokesperson said it was prioritising returning power to hospitals, San Juan's airport, water pumping systems and financial systems.
The power authority, which has been in bankruptcy since last July, has struggled to stay out of the headlines since the island was hit in September by the worst storm in 90 years.
Residents have suffered multiple blackouts since Category 4 Maria, and 40,000 people were still without power at the time of Wednesday's blackout.
"Seven months after Maria, we are back where Maria left us," Cynthia Garcia Coll, a professor at Carlos Albizu University in San Juan, told CNN.
The US territory's first island-wide outage comes less than a week after a fallen tree knocked out service to 870,000 customers.
Hurricane Maria caused the largest blackout in US history, according to research consultancy the Rhodium Group.
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