The newspaper said the biggest killer is premature birth, the major cause of death for babies and young children, with violence in second place.
In 2010, the death rate for those less than 18 years of age was 120 per 100,000, the newspaper said. Philadelphia had the second-highest rate, 95.7 per 100,000.
"This is a public health emergency in the city of Detroit," Dr. Herman Gray, executive vice president of pediatric health services for the Detroit Medical Center, said. "We are losing our future in really socially unacceptable ways."
In 2010, Detroit and Cleveland had the highest infant mortality rates among big U.S. cities, with 13.5 babies dying for every 1,000 live births. This was higher than the mortality rate in Romania, Botswana and Panama.
That year, 32 children and teenagers died from violence. The newspaper found the death rate from violence increased significantly when the U.S. economy slumped in 2008, making Detroit, already one of the country's poorest cities, even poorer.
The News survey found Detroit children are also more likely than those in other major cities to die from influenza, asthma and other diseases.