Fossil fuel carbon dioxide (CO2) emissions (ffCO2) constitute the majority of greenhouse gas emissions and are the main determinant of global climate change. The COVID-19 pandemic caused wide-scale disruption to human activity and provided an opportunity to evaluate our capability to detect ffCO2 emission reductions. Quantifying changes in ffCO2 levels is especially challenging in cities, where climate mitigation policies are being implemented but local emissions lead to spatially and temporally complex atmospheric mixing ratios. Here, we assess ffCO2 emission patterns associated with pandemic-induced changes to human activity using direct observations of on-road CO2 mole fractions in the Los Angeles (LA) urban area and analyses of the radiocarbon (14C) content of annual grasses collected by community scientists throughout California, USA. With COVID-19 mobility restrictions in place in 2020, we observed a significant reduction in ffCO2 levels across California, especially in urban centers. In LA, on-road CO2 enhancements were 60 ± 16% lower than the corresponding period of 2019 and rebounded to pre-pandemic levels by 2021. Plant 14C analysis indicated ffCO2 reductions of 5 ± 10 ppm in 2020 relative to pre-pandemic observations in LA. However, ffCO2 emission trajectories varied substantially by region and sector as COVID-related restrictions were relaxed. Further development of these techniques could aid efforts to monitor decarbonization in cities, especially in developing countries without established CO2 monitoring infrastructure.