All the victims were in close proximity to each other in the small town of Arkabutla, Mississippi about 45 miles (72km) south of Memphis, in neighboring Tennessee.
Three victims were found dead inside two houses, while others were found inside a store, in a car and on a roadway.
Police confirmed to BBC News they have a suspected gunman in custody.
The man is believed to have acted alone, although his motive is not yet known, Mississippi Governor Tate Reeves tweeted on Friday.
“I will ensure that the full resources of the state are available to law enforcement as we continue to investigate the situation,” Mr Reeves wrote.
The gunman first entered a local store and shot a man around 11:00 local time (17:00 GMT), Tate County Sheriff Brad Lance told Action News 5.
He then went to a nearby home where he shot a woman dead and injured her husband, the sheriff said.
Mr Lance added that deputies spotted the suspect inside a car matching witnesses’ descriptions and were able to apprehend the suspect after a brief car chase.
The car chase reportedly ended when the suspect pulled into the driveway of a home on Arkabutla Dam Road that is believed to be where he lives.
Police went on to find four more victims on the same roadway, two found inside a home and two others outside, reports said.
The suspect was “dressed in camouflage with a long gun”, an eye-witness told local reporter Kelli Cook.
A primary and secondary school in nearby Coldwater were placed in lockdown during the incident. All students in both schools are safe, the Coldwater Elementary School said on its Facebook page.
Another witness – Ethan Chase, a 19-year-old local resident – told WREG-TV that he had seen the gun-toting suspect and that he came outside to check the pulse of the victim who died inside their vehicle.
“This… doesn’t happen out here,” he said. “This is supposed to be a peaceful place.”
Arkabutla is home to less than 300 people, according to 2020 census data. A nearby reservoir known as Arkabutla Lake is a popular fishing and recreation spot for locals.
The Mississippi Bureau of Investigation has been asked to assist with the investigation.
Friday’s incident marks the 73rd mass shooting since the year began, according to the Gun Violence Archive (GVA) non-profit research database. GVA defines a mass shooting as an incident in which four or more people are injured or killed.