Officers responded just after 12.30am to the Avondale neighbourhood and found 21-year-old Antonio Blair with gunshot wounds, police said in a statement.
He was taken to University Hospital and died there, they said.
Three other gunshot victims were also taken to the hospital.
At about 2.15am, officers responded to a report of gunfire in the Over-the-Rhine neighbourhood where 10 people were shot, police said.
One died at the scene and another at the University of Cincinnati Medical Centre.
They were identified in a statement as 34-year-old Robert Rogers and 30-year-old Jaquiez Grant.
Three people were shot at about midnight in the Walnut Hills neighbourhood, about a block away from the Harriet Beecher Stowe house, police said.
News outlets reported the shootings took place within 60 to 90 minutes of each other but Assistant Police Chief Paul Neudigate told reporters they “seem to be separate independent incidents but horrific and tragic”.
Police did not immediately provide details about the fourth fatal shooting but television news reports indicated one person was shot later on Sunday morning – an 18th person shot – on the city’s West End and pronounced dead at the scene.
No suspect information was immediately available.
We all have a moral obligation to stop the violence and stop the killing in our communities
Mr Neudigate said before the fourth shooting was announced: “One extremely violent night in the city of Cincinnati.
“Looking at possibly 17 victims, up to four that could be fatal at this time. Why? That’s going to be the question.”
Later on Sunday, Cincinnati’s police chief called the level of violence “unacceptable.”
“I am calling on all citizens of this great city to say enough is enough,” Eliot Isaac said in a statement.
“We must not sit by silently and say we can’t do anything to end gun violence.
“We all have a moral obligation to stop the violence and stop the killing in our communities.”
Police said the department will shift officers from other assignments to beef up the number of uniformed officers in the affected communities and will call on federal prosecutors and the Bureau of Alcohol, Tobacco, Firearms and Explosives “to focus on repeat shooters and aggressively bring illegal gun charges”.
Mayor John Cranley called it “senseless gun violence that ruined lives and will cause immeasurable suffering” at a time the city is facing “unprecedented circumstances and challenges” in fighting crime during the Covid-19 pandemic.
He said the city has experienced a rise in coronavirus cases as people gather in private homes and public places when the bars close.
“Guns are far too prevalent at these gatherings,” he said in a statement.
“Please do not attend gatherings because you could end up as an innocent victim.”
But he stressed those firing are responsible for the shootings – which he called “attempted or actual murder” – and vowed to bring them to justice.
“I am also calling on everyone to help put an end this culture of resolving personal disputes with guns as well as to reduce the far too prevalent availability of illegal guns on our streets,” he said.
“The very sad reality is people are getting in trouble when they have nowhere to go and nothing to do.”
In July, the Enquirer reported the city had experienced a rise in shootings and homicides from gun violence during the first half of the year compared with the same time period in 2019.