In this work, we use observations and experimental emissions in a version of NOAA's National Air Quality Forecasting Capability to show that the COVID-19 economic slowdown led to disproportionate impacts on near-surface ozone concentrations across the contiguous U.S. (CONUS). The data-fusion methodology used here includes both U.S. EPA Air Quality System ground and the NASA Aura satellite Ozone Monitoring Instrument (OMI) NO2 observations to infer the representative emissions changes due to the COVID-19 economic slowdown in the U.S. Results show that there were widespread decreases in anthropogenic (e.g., NOx) emissions in the U.S. during March–June 2020, which led to widespread decreases in ozone concentrations in the rural regions that are NOx-limited, but also some localized increases near urban centers that are VOC-limited. Later in June–September, there were smaller decreases, and potentially some relative increases in NOx emissions for many areas of the U.S. (e.g., south-southeast) that led to more extensive increases in ozone concentrations that are partly in agreement with observations. The widespread NOx emissions changes also alters the O3 photochemical formation regimes, most notably the NOx emissions decreases in March–April, which can enhance (mitigate) the NOx-limited (VOC-limited) regimes in different regions of CONUS. The average of all AirNow hourly O3 changes for 2020–2019 range from about +1 to −4 ppb during March–September, and are associated with predominantly urban monitoring sites that demonstrate considerable spatiotemporal variability for the 2020 ozone changes compared to the previous five years individually (2015–2019). The simulated maximum values of the average O3 changes for March–September range from about +8 to −4 ppb (or +40 to −10%). Results of this work have implications for the use of widespread controls of anthropogenic emissions, particularly those from mobile sources, used to curb ozone pollution under the current meteorological and climate conditions in the U.S. •Observations and chemical transport modeling are used to quantify COVID-19 lockdown impacts on ozone pollution in the U.S.•Widespread emissions decreases lead to widespread ozone decreases in rural regions, but local increases in urban regions.•There is considerable spatiotemporal variability for the 2020 ozone changes compared to the previous five years. Plain Language Summary: This study uses observations and chemical transport modeling to calculate the changes in air pollution, namely for ground-level ozone, or “smog”, which are related to the COVID-19 mobility restrictions and traffic emissions changes in the U.S. between March and September 2020. Results show that there are widespread decreases in emissions during March–April, but also that the changes are highly variable, while shifting to smaller emission decreases or even increases for a number of U.S. states by June–September. The changes in emissions and characteristics of ozone formation lead to spatially variable impacts on ozone concentrations, with widespread decreases in the rural areas, and some local increases near the major cities of the U.S. The observations and modeling suggest that the areas of increased ozone concentration becomes more extensive in the late spring and summer, “ozone-season” months of June–September. Results of this work are important to strategies used to control emissions and ozone pollution in the U.S.