ImportanceA loophole in US gun policy is that people can purchase guns from private sellers without going through any background check. Some states have addressed this loophole by requiring universal background checks for all gun sales, either at the point of sale or through a permit system; however, most studies on the effectiveness of universal background checks have not analyzed these 2 policy mechanisms separately.ObjectiveTo assess the association of point-of-sale background check law and gun permit law, separately, with firearm homicide rates from 1976 through 2022 using the same methods and model specification.Design, Setting, and ParticipantsThis cross-sectional study used a difference-in-differences, fixed-effects regression model to evaluate firearm laws and firearm homicide rates in 48 states from 1976 through 2022. Data were obtained for 48 states except New Hampshire and Vermont and were analyzed in January 2024.ExposuresImplementation of either the law requiring a universal background check at point of sale for all firearms without a permit or the laws combining universal background checks and a state permit requirement for all gun purchasers.Main Outcomes and MeasuresAnnual, state-specific rates of firearm homicide per 100 000 people.ResultsFrom 1976 through 2022, 12 states adopted the universal background check laws without permitting requirements and 7 states implemented gun permit laws covering all firearms. The mean (SD) firearm homicide rate was 4.3 (0.1) per 100 000 people. Universal background checks for all firearms alone (without a state permitting system) were not associated with overall homicide rates (percentage change, 1.3%; 95% CI, −6.9% to 10.4%) or firearm homicide rates (percentage change, 3.7%; 95% CI, −5.3% to 13.6%). A law requiring a permit for the purchase of all firearms was associated with significantly lower overall homicide rates (percentage change, −15.4%; 95% CI, −28.5% to −0.01%) and firearm homicide rates (percentage change, −18.3%; 95% CI, −32.0% to −1.9%).Conclusions and RelevanceThis cross-sectional study found that universal background checks alone were not associated with firearm homicide rates, but a permit requirement for the purchase and possession of firearms was associated with substantially reduced rates of firearm homicide. The findings suggest that combining universal background checks and permit-to-purchase requirements is an effective strategy for firearm-related fatality reduction.