The quake struck in one of Japan's main manufacturing heartlands, home to companies including Panasonic Corp., Nintendo Co. and Keyence Corp, and plants across the area were halted as firms assessed the damage.
Local police said a girl, aged nine, had died in the city of Takatsuki, north of Osaka city.
The quake hit western Japan early Monday, but there were no immediate reports of major damage or risk of tsunami waves, officials said. Television images showed passengers getting off trains onto the tracks between stations.
The Japan Meteorological Agency is warning that over one week there may be aftershocks that have around the same seismic intensity as Monday's quake, which registered lower 6 on the Japanese scale of 7.
Japanese media including public broadcaster NHK said collapsing walls had killed an 80-year-old man and a 9-year-old girl, and that another man in his 80s was killed after being crushed by a toppling bookcase.
Osaka prefecture, which includes the city and surrounding areas, has a population of 8.8 million.
The epicenter of Monday's quake was just north of Osaka city at a depth of 13 km (8 miles), said the Japan Meteorological Agency.More news: Dollar and stocks slip as Trump hits China with tariffs
Japanese government spokesman Yoshihide Suga says there were no reports of major damage as of 8:30 a.m.
NHK showed footage of firefighters tackling a blaze that ripped through a home north of Osaka.
The magnitude 6.1 natural disaster near the major city of Osaka killed three people, toppled concrete walls and store shelves and temporarily knocked out some power and water supplies. "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.
Kepco said its Fukui nuclear plants were operating normally.
Japan sits on the so-called Ring of Fire, one of the most active seismic zones in the world, and experiences earthquakes frequently, which is why most infrastructure is specially created to withstand earthquakes. In 1995, a magnitude 6.9 quake killed more than 6000 people when it struck in neighbouring Kobe.
It also sent three reactors into meltdown at the Fukushima nuclear plant, causing Japan's worst postwar disaster and the most serious nuclear accident since Chernobyl in 1986.