Transport was disrupted and trains stopped amid power outages during the morning commute as the natural disaster struck at 8.a.m. local time (23.00 Sunday, UTC) at a depth of about 13 kilometers (8.1 miles). Japanese media reported one of the likely victims is a 9-year-old girl found at a school.
Bloomberg reported plants across the area were halted as firms assessed the damage.
The Fire and Disaster Management Agency said the number of the injured had risen to 91 about three and a half hours after the quake struck the region. A man in his 80s died in the collapse of a concrete wall in Osaka city.
Japanese government spokesman Yoshihide Suga said there were no reports of major damage as of 8.30am (local time).
The magnitude-6.1earthquake, initially measured at 5.9, struck the region, 400 kilometres west of Tokyo, during the morning commute.
Three people were confirmed dead and nearly 100 injured after a strong quake hit Osaka on Monday morning, rattling one of Japan's industrial heartlands and halting trains and factories across the region.
The operation of bullet trains running through the prefecture was suspended following the quake but service was resumed shortly afterward after no safety problems were detected.
Kim Jong-un writes Putin a note and receives invite to Russian Federation
It seemed like the message from the Trump administration had been, you know, the trade in North Korea are linked. On Tuesday, Mr Trump and Kim signed a document which stipulates for the denuclearisation of North Korea.
At 13 kilometers (8.1 miles) it was relatively shallow, and caused heavy shaking that registered a lower 6 on the Japanese scale of 7. "Almost all of the dishes fell and shattered on the floor", Kaori Iwakiri, a 50-year-old nurse in Moriguchi - just north of Osaka city - said.
The area north of Osaka was the hardest hit, the agency said.
Multiple small aftershocks followed the quake, and an official from Japan's meteorological agency warned residents to remain on guard.
Besides electricity outages, at least one house caught fire and several major water pipes burst following the quake, according to footage shown by local TV.
The vehicle manufacturer Daihatsu said it had suspended operations at its plants in Osaka and nearby Kyoto, while the consumer electronics firm Sharp said its factories were operating normally.
"We were sleeping and it woke us up abruptly", said Kate Kilpatrick, 19, who was staying in a hotel in Osaka when the quake hit.