This study examines how driving patterns (distance and conditions) and the electricity generation supply interact to impact well-to-wheel (WTW) energy use and greenhouse gas (GHG) emissions of plug-in hybrid electric vehicles (PHEVs). The WTW performance of a PHEV is compared with that of a similar (nonplug-in) gasoline hybrid electric vehicle and internal combustion engine vehicle (ICEV). Driving PHEVs for short distances between recharging generally results in lower WTW total and fossil energy use and GHG emissions per kilometer compared to driving long distances, but the extent of the reductions depends on the electricity supply. For example, the shortest driving pattern in this study with hydroelectricity uses 81% less fossil energy than the longest driving pattern. However, the shortest driving pattern with coal-based electricity uses only 28% less fossil energy. Similar trends are observed in reductions relative to the nonplug-in vehicles. Irrespective of the electricity supply, PHEVs result in greater reductions in WTW energy use and GHG emissions relative to ICEVs for city than highway driving conditions. PHEVs charging from coal facilities only reduce WTW energy use and GHG emissions relative to ICEVs for certain favorable driving conditions. The study results have implications for environmentally beneficial PHEV adoption and usage patterns.