Most 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 30 of those who died were found inside cars, with another 17 next to the vehicles, on one road leading on to the IC8 motorway.
Media in Portugal said the fire is no closer to being contained despite about 600 firefighters working to put it 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.