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.
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.
Another 11 died in a village next to the motorway, Mr Gomes said.
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.
Six firefighters are seriously wounded, national broadcaster RTP said, and two are reported missing.
The Correio do Manhã warned that many areas hit by the fire had not yet been reached by authorities, so the death toll was likely to increase.