Japan's Fire and Disaster Management Agency said two people were found with no vital signs and 41 others had been injured.
The Japan Meteorological Agency said a quake with preliminary magnitude of 5.9 struck Monday around 8am.
Rina Miyake, a 9-year-old girl, died on her way to school after a wall several dozens of meters long around a swimming pool collapsed in Takatsuki.
The victims, who have yet to be named, were described as being in a state of "cardiopulmonary arrest" - a term Japanese media use until doctors have conducted formal examinations.
Dozens of domestic flights in and out of Osaka were grounded, while train and subway service in the Osaka area, including bullet trains, were suspended to check for damage. Passengers were seen exiting trains on the tracks between stations.
Kansai Electric said on its website that around 170,000 homes in the Osaka region were without power.
A number of people were trapped in elevators, windows broke and and small fires were set off in buildings. It toppled bookcases in homes and scattered goods on shop floors.
Senior government officials are gathering for an emergency meeting at the Prime Minister's office, broadcaster NHK reported.
Strong earthquake strikes Japanese city
The quake, which was recorded at a depth of 13km, left more than 170,000 households without power in Osaka prefecture and neighbouring Hyogo prefecture, where an natural disaster killed more than 6,400 people in the city of Kobe in January 1995.
People walk on a bridge while train and subway service were suspended to check for damage after an quake in Osaka.
Daihatsu Motor Co, a unit of Toyota Motor Corp, said it had suspended production at its factories in Osaka and Kyoto while it checked for damage. Most of the injured were in Osaka - Japan's No. 2 city bustling with businesses.
Takuya Nishimura, an associate professor of geodetics at Kyoto University, said there was a possibility that the quake had occurred at the eastern end of a fault extending from the northern part of the prefecture to Awaji Island in Hyogo Prefecture.
The quake disrupted some of Japan's usually meticulous train services from Osaka to other major cities including Tokyo and Nagoya. "The whole world was aggressively shaking", she said. I thought it was a nightmare because I was so confused.
Kate Kilpatrick, visiting Japan for the first time from the United States, said alarms went off nearly immediately in the Osaka hotel she was staying and a loudspeaker told guests to stay away from windows.
"It was not as bad as the Kobe quake", he told the Associated Press from Osaka.
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