Plants in urban ecosystems are exposed to many pollutants and higher temperatures, CO2 and nitrogen deposition than plants in rural areas. Although each factor has a detrimental or beneficial influence on plant growth, the net effect of all factors and the key driving variables are unknown. We grew the same cottonwood clone in urban and rural sites and found that urban plant biomass was double that of rural sites. Using soil transplants, nutrient budgets, chamber experiments and multiple regression analyses, we show that soils, temperature, CO2, nutrient deposition, urban air pollutants and microclimatic variables could not account for increased growth in the city. Rather, higher rural ozone (O3) exposures reduced growth at rural sites. Urban precursors fuel the reactions of O3 formation, but NO(x) scavenging reactions resulted in lower cumulative urban O3 exposures compared to agricultural and forested sites throughout the northeastern USA. Our study shows the overriding effect of O3 despite a diversity of altered environmental factors, reveals 'footprints' of lower cumulative urban O3 exposures amidst a background of higher regional exposures, and shows a greater adverse effect of urban pollutant emissions beyond the urban core.