Recent estimates of blue (Balaenoptera musculus) and humpback (Megaptera novaeangliae) whale ship-strike deaths on the US west coast are above the Potential Biological Removal limit determined by the National Marine Fisheries Service. Beginning in 2015, the National Oceanographic and Atmospheric Administration requested voluntary Vessel Speed Reductions (VSR) in the designated shipping routes off San Francisco, California, USA, in order to decrease whale mortality from ship strikes. We applied a ship strike model based on whale density and Automatic Identification System (AIS) vessel data. We bootstrapped speeds from vessels that transited when no VSR was in place to assess the effect of the VSR on strike mortality rates. Finally, we calculated the expected mortality for hypothetical compliance scenarios by programmatically imposing speed caps. Average predicted mortality for the region was 2.7 blue whales and 7.0 humpback whales in a 4 month period. Compared to years prior to the VSR (2012−2014), vessel speeds during the VSR were slower. This lowered blue whale deaths within the shipping lanes by 11–13% and humpback whale deaths by 9–10% in 2016−2017. If 95% of mariners adhered to recommended 10 knot (kn) limits in the shipping lanes alone, we predicted twice as many blue whale and 3 times as many humpback whale deaths would be avoided relative to current adherence. Adding a 10 kn speed limit (with 95% coope ration) at the ends of each of the lanes would result in about 5- and 4-fold reductions in blue whale and humpback whale mortality, respectively, relative to current practices. Our approach can evaluate ship strikes and mitigation measures for whale populations around the globe.