(bbc) -- Many died while trying to flee the Pedrógão Grande area, 50 km (30 miles) south-east of Coimbra, in their cars, according to the government.
Several firefighters are among the 59 people injured.
"Unfortunately this seems to be the greatest tragedy we have seen in recent years in terms of forest fires," said Prime Minister Antonio Costa.
The death toll could rise further, he said.
Secretary of State for the Interior Jorge Gomes said that three people died from smoke inhalation and 18 people travelling in four cars died on the road linking Figueiró dos Vinhos to Castanheira de Pera.
Media in Portugal said the fire is no closer to being contained despite about 600 firefighters working to put them out.
Among the 59 injured was an eight-year-old girl with burns found wandering alone close to the fire, the Correio do Manhã newspaper reported.