The 6.8-magntiude quake hit a narrow strait between the heavily populated island provinces of Negros and Cebu around lunchtime, with aftershocks nearly as strong causing further panic throughout the day.
The worst-hit area appeared to be Guihulngan, a coastal city in Negros close to the quake's epicentre, with 39 people confirmed killed there, according to local military commander Colonel Francisco Patrimonio.
He and local police said most of the victims had died as landslides buried homes, while others in the city of 100,000 people died as houses collapsed under the pressure of the quake itself.
"Some private homes collapsed along with our court house and parts of the public market. We got people out of the buildings but we could not evacuate the homes," police chief Senior Inspector Alvin Futalan told AFP.
Four other people were confirmed killed in other parts of Negros, where power outages were widespread and bridges as well as other vital infrastructure had been damaged, according to Patrimonio.
He and other government officials warned the death toll may rise, with reports of dozens of other people injured or missing in Guihulngan and nearby areas.
However, they said it was impossible to determine the exact number of missing, as power and many phone lines in the region were down and roads to the mountainous areas were impassable because of the landslides.
Patrimonio said that authorities were having to deal with looting, as well as the immediate rescue efforts, as some people took advantage of the chaos.
"Looting is now rampant in Guihulngan which forced us to commit (more troops) with the Philippine national police," he said.
In Cebu, a popular tourist destination and the country's second biggest city with 2.3 million residents, hotel guests scrambled to higher floors as unfounded rumours that a huge tsunami was bearing down spread by text message.
"There is news going around of tsunami waves, so we are doing our best to keep everybody calm," Barbi Patino, a spokesman for the 17-story Parklane International Hotel, told AFP shortly after the quake struck.
Civil defence chief Benito Ramos said the violent shaking of buildings in Cebu -- 50 kilometres (31 miles) from the epicentre -- led to broken windows and cracks on some walls.
But no high-rises sustained major damage and no deaths were reported in in the city.
Pedro Baldomino, a student in Cebu, said he saw many office workers leaving their buildings after a public announcement on radio warned people to brace for expected aftershocks.
"I was having lunch when the ground shook. Water spilled from glasses and plates clanked. Some of the diners rushed outside, some of us stayed underneath the tables," he said.
Almost four hours after the quake struck, a strong 6.2-magnitude aftershock hit the central Philippines, and then another struck measuring 6.0, causing further panic.
Over 200 less-powerful aftershocks were detected throughout the day, said provincial disaster monitoring executive director Angelo Tiongson.
Philippine government seismologists initially raised a precautionary tsunami alert over the quake, but lowered it two hours later.
The Hawaii-based Pacific Tsunami Warning Centre said there was no danger of a widespread destructive tsunami.
The Philippines sits on the Pacific "Ring of Fire" -- a belt around the Pacific Ocean where friction between shifting tectonic plates causes frequent earthquakes and volcanic activity.