The study, which appears in the American Journal of Public Health, challenges the National Rifle Association's claim that increased gun ownership does not lead to higher levels of gun violence.
Covering 30 years from 1981 and all 50 US states, it determined that for every one percentage point in the prevalence of gun ownership in a given state, the firearm homicide rate increased by 0.9%.
In the absence of state-level data on household gun ownership, the study used a proxy variable - the percentage of a state's suicides committed with a firearm - that has been validated in previous research.
The study, led by Boston University community health sciences professor Michael Siegel, is the first of its kind since the December 2012 mass shooting of 20 children at Sandy Hook Elementary School in Newtown, Connecticut.
"In the wake of the tragic shooting in Newtown ... many states are considering legislation to control firearm-related deaths," said Siegel in a statement.
"This research is the strongest to date to document that states with higher levels of gun ownership have disproportionately large numbers of deaths from firearm-related homicides," he said.
"It suggests that measures which succeed in decreasing the overall prevalence of guns will lower firearm homicide rates."
The study found that, over three decades, the mean estimated percentage of gun ownership ranged from a low of 25.8% in Hawaii to a high of 76.8% in Mississippi, with a national average of 57.7%.
The mean age-adjusted firearm homicide rate stretched from 0.9% per 100,000 in New Hampshire to 1.8% in Louisiana, with an average for all states of four per 100 000.
The study also acknowledged a long-term decline in firearm homicide for all states, from 5.2 per 100 000 in 1981 to 3.5 per 100 000 in 2010.
Firearms were involved in 11 078 homicides of the 16 259 homicides in the United States in 2010, the latest year for which data is available, according to the Centres for Disease Control and Prevention.