The shooting occurred at Cameo Night Club just after 1 a.m. ET.
Several people are undergoing surgery, Cincinnati Police Sgt. Eric Franz told CNN.
Police do not have any suspects in custody, but are interviewing witnesses.
Police believe "multiple shooters" were involved, Franz said.
While the motive is unclear, there's no reason to suspect terrorism at this point, he said.
Cameo Night Club hires police officers for extra security. Two officers were stationed at the club's entrance and another two in the parking lot, Franz said.
'Long night'
Assistant Police Chief Paul Neudigate said that several victims have life-threatening injuries.
"We are in the middle of a very horrific situation that occurred at the nightclub with multiple victims," Neudigate said. "It's going to be a long night for our homicide units to investigate."
Neudigate described it as a "chaotic crime scene," and said they are looking for witnesses, many of whom took off when the shooting started.
"Many of the witnesses fled, but everyone that we can identify is being interviewed," he said.
Some of the injured drove themselves to area hospitals, police said.