Air toxics are an important category of air pollutants that are known to cause adverse health effects, including increased cancer risk. Regulatory efforts at federal, state, and local levels have aimed to decrease air toxics emissions over the past several decades. This study evaluated trends in air toxics cancer risks in Southern California using data from 1998 to 2018. We estimated air toxics cancer risk for each of four iterations of the South Coast Air Quality Management District’s Multiple Air Toxics Exposure Study, which included at least one year of measurements at 10 stations and air toxics modeling for each iteration. Cancer risks were calculated using the measured and modeled air toxics concentrations averaged over a one to two year period and multiplied by the corresponding cancer potency factor and combined exposure factor that accounted for multiple exposure pathways and children’s increased sensitivity to the health effects of air pollution. We examined temporal trends in overall air toxics cancer risks and evaluated changes in the air toxics species that contributed most to cancer risk in the region. Both measurement and modeling results show that air toxics cancer risk in Southern California decreased by more than 80% between 1998 and 2018, including a decrease of about 50% from 2012 to 2018. Diesel particulate matter was the main risk driver, followed by benzene, 1,3-butadiene, and formaldehyde. We found that more densely populated communities showed larger decreases than sparsely populated areas. The substantial decrease in air toxics levels over this 20-year period points to the success of air pollution policies aimed at addressing air toxics emissions and can inform future policy efforts to further reduce air toxics health impacts.