Japanese Prime Minister Sanae Takaichi said the number of casualties and extent of the damage in the area - which was devastated by a tremblor a decade ago - were still being assessed.
"We have already been informed that people have been injured. Power outages and fires have occurred in some areas, and there has also been damage to roads and bridges and the collapse of buildings," Takaichi said told reporters on Tuesday.
"I ask everyone to take action to protect themselves, including evacuating to a safe location."
One hospital had reported more than 50 injuries, public broadcaster NHK said.
Several people on a high-speed train at the time of the quake were also injured, Nikkei newspaper said.
People were trapped inside an Aeon shopping centre rocked by an explosion that occurred after the earthquake, emergency services said.
An Aeon spokesperson said customers and employees were evacuated right after the initial quake and the exact cause of the ensuing explosion was unclear.
Kazuya Tsurunaga told broadcaster TBS he heard the explosion while cleaning up dishes broken by the earthquake inside a pub about 300 metres from the Aeon mall.
"It was a huge impact," he said.
"A large cloud of smoke billowed up, and because the wind happened to be blowing and the wind direction was towards the shop, the area around us was in a state like volcanic ash was falling."
Several other buildings were also on fire or partially collapsed, according to footage from NHK, while large cracks appeared on major roads, including an elevated highway.
TSMC, the world's largest contract chipmaker, evacuated workers from its plant in the area as a precaution, and Sony and Fujifilm also evacuated staff from their plants in the area.
About 300,000 people were instructed to go to evacuation centres, the disaster management agency said.
The quake's epicentre was about 20km south of Kumamoto, central Kyushu island's largest city with a population of about 700,000.
Residents in the areas that felt the biggest tremors must beware of further strong quakes for about a week, as well as the risk of landslides, an official for the Japan Meteorological Agency said.
Japan is one of the world's most earthquake-prone countries, with a tremor occurring at least every five minutes.
Located along 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.
A tsunami warning was issued immediately after Tuesday's quake, but was later lifted.
Kyushu Electric Power said 48,000 homes had lost power as a result of the latest quake, while railway company JR Kyushu said it had suspended services, including its high-speed bullet trains.
Kumamoto airport also shut its runway, as airlines diverted and cancelled flights.
Telecoms operators KDDI and Docomo said there was disruption to their mobile phone services due to power shortages and transmission-line failures.
No irregularities were reported at the nuclear power stations in the area, Japan's nuclear regulation authority said.
A massive earthquake in Kumamoto 10 years ago killed 275 people and injured a further 2739, according to an official count, and damaged thousands of buildings including the city's castle, a top tourist site.
Some portions of the stone walls at the castle also collapsed as a result of Tuesday's quake, an official at the castle's office said.
