Humanity’s emissions of greenhouse gases have warmed the planet to the point that Earth may already be passing the 1.5 °C Paris Agreement threshold. Without stringent reductions in emissions of greenhouse gases, it is becoming increasingly likely that Earth will exceed 2 °C global warming by the end of the century. Should Paris Agreement global warming levels be exceeded, future periods of net-negative carbon dioxide emissions would be required to reverse global warming and satisfy the Paris Agreement goals. However, the implications of that for regional climates remain uncertain. We investigate drivers and uncertainties in regional climate change using the SSP5-3.4 overshoot scenarios that include extended periods of net-zero anthropogenic carbon dioxide emissions after overshoot and net-negative emissions. We find that model differences in evolution of regional climate during the net-zero carbon dioxide emissions period are far greater than model differences during the net-positive and net-negative emissions periods of the overshoot scenario. However, the diversity in models’ climate projections during the post-overshoot net-zero emissions period may be partially explained by changes in large-scale sea surface temperature and atmospheric pressure gradients. By further exploring sources of uncertainty in climate projections throughout the overshoot scenario, we find that the uncertainty from simulated internal variability can far outweigh the differences in climate projections between models, especially during the extended net-zero emissions period of the scenario.