The power cut plunged the capital Caracas into almost complete darkness during rush hour on Thursday, before extending to other areas.
The government of President Nicolás Maduro has blamed the opposition, accusing them of sabotage.
It comes amid rising tensions over opposition efforts – backed by the US and some Latin American countries – to remove Mr Maduro from power.
Mr Maduro accuses opposition leader and self-declared interim president Juan Guaidó of trying to mount a coup with the help of “US imperialists”.
Mr Guaidó said the blackout was a matter of “chaos, concern and anger” and “evidence of the usurper’s inefficiency”.
“Light would return” once Mr Maduro was removed from power,” he said.
US Secretary of State Mike Pompeo also weighed in, blaming the “Maduro regime’s incompetence”.
“No food. No medicine. Now, no power. Next, no Maduro,” he tweeted.
The lack of electricity has caused flights to be diverted from the main airport in Caracas, where thousands of workers were forced to walk home.
Venezuela depends on its vast hydroelectric infrastructure, rather than its oil reserves, for its domestic electricity supply.
However, decades of underinvestment have damaged the major dams and sporadic blackouts are commonplace.
What’s the background to the political crisis?
Mr Maduro took over the presidency when his late mentor Hugo Chavez died in 2013. In recent years Venezuela has experienced an economic collapse, with severe food shortages and inflation reaching at least 800,000% last year.
The Maduro government is becoming increasingly isolated as more and more countries blame it for the economic crisis, which has prompted more than three million people to leave Venezuela.
Mr Guaidó, who leads the opposition-controlled National Assembly, declared himself interim president on 23 January and has been at loggerheads with President Maduro ever since.
He has been recognised as interim president by more than 50 countries but Mr Maduro retains the support of his close allies Russia, Cuba and China among others.
