Eight people were pulled from the rubble of a partially collapsed shopping mall near the city of Kumamoto that was torn apart by an explosion about an hour after Tuesday's earthquake. Of them, three have died.
Another three workers at the shopping centre remained unaccounted for after checks of the roughly 2700 staff, Akio Yoshida, president of mall operator Aeon, told a reporters on Wednesday.
Customers had been evacuated right after the initial quake.
"Even now, there are people waiting to be rescued, and this is a race against time," Prime Minister Sanae Takaichi told reporters in Tokyo.
"We will marshal all available resources on the ground to save and rescue as many people as possible."
Overall, 13 people were killed, five were in cardiac arrest and at least eight others seriously injured, authorities said.
Hospitals were reported to be treating dozens of other patients.
Authorities are investigating a possible gas explosion at the Aeon mall.
Rescuers reported smelling gas inside the building but the cause of the incident was still under investigation, said Japan's top government spokesperson, Minoru Kihara.
"I thought a bomb had gone off," Takateru Sonoda, 41, who runs a combined hair salon and cafe near the mall, told Jiji Press.
"There were people calling on others to evacuate and sirens were ringing out. Nearby roads were gridlocked, it was a state of panic."
Emergency fire rescue teams, police and about 170 army personnel were focusing on areas of the building where calls for help had been received.
More than 4500 soldiers have been deployed to help across the quake zone.
Five people died and another two were injured at a Nippon Paper Industries factory where the quake knocked over a chimney, public broadcaster NHK said, with a local government official saying earlier that seven were missing in the incident.
Across the prefecture, which also suffered a deadly earthquake a decade ago, about 260,000 people were instructed to go to evacuation centres, authorities said.
The quake's epicentre was about 20km south of Kumamoto City, central Kyushu's largest city with a population of about 700,000.
The quake was followed by more than 100 aftershocks.
In nearby Yatsushiro city - among the hardest-hit areas - many homes had damaged roofs and a handful of buildings collapsed.
Roads leading to the coastal town were cracked and buckled in places, and many businesses remained shuttered.
Part of a bridge had collapsed into the Kumagawa River, drawing a steady trickle of curious residents to the site.
Authorities have warned residents in the areas that felt the biggest tremors to be on alert for further strong quakes for about a week, as well as for the risk of landslides.
On Japan's seismic intensity scale, Tuesday's tremor measured the highest level of 7.0 in some areas.
With more than 36,000 homes still without power as temperatures soar to about 34C on Wednesday, authorities also warned about the risk of heat stroke.
Several passengers aboard high-speed trains at the time of the quake were injured, said operators, who immediately suspended all services after the jolt.
Public attention was focused on the collapse of the Aeon shopping centre, the largest in the prefecture.
One side of the mall, which houses about 200 stores, was torn away, exposing steel beams and strewing debris across a car park.
Some major companies with plants in the area, including Renesas Electronics, Sony, Tokyo Electron and Honda, have suspended operations at their plants.
TSMC, the world's largest contract chipmaker, evacuated workers from its local plant as a precaution but said it had begun resuming operations late on Tuesday.
Located on the "Ring of Fire" of volcanoes and oceanic trenches partly encircling the Pacific Basin, Japan accounts for about 20 per cent of the world's earthquakes of magnitude 6.0 or more.