The pilot and a TV meteorologist were the only ones killed in the crash along Interstate 77 in the city's Yorkmount area, which is located about six miles southwest of downtown Charlotte.
Mecklenburg County EMS service said on Twitter that two people were pronounced dead at the scene.
Police said that no vehicles were involved in the incident.
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WBTV identified those killed as employees: pilot Chip Tayag and meteorologist Jason Myers.
"The WBTV family is grieving a terrible loss. Our news helicopter Sky3 crashed midday Tuesday with two of our colleagues on board," a WBTV statement read.
Charlotte Metropolitan Police Department Chief Johnny Jennings said the helicopter pilot appeared to have done everything in his power to avoid hitting drivers on the interstate.
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Jennings said Tayag, who had more than 20 years of piloting experience, is a hero in his eyes.
Myers graduated from North Carolina State University and worked as a weather observer at Raleigh-Durham International Airport before starting his broadcast meteorology career, according to his WBTV bio.
The Federal Aviation Administration said the helicopter was a Robinson R44. FAA and National Transportation Safety Board will investigate what caused the aircraft to crash.
2 killed in helicopter crash near Interstate 77 in south Charlotte
The Associated Press contributed to this story.