A 56-year time series of human plague cases (Yersinia pestis) in the western United States was used to explore the effects of climatic patterns on plague levels. We found that the Pacific Decadal Oscillation (PDO), together with previous plague levels and above-normal temperatures, explained much of the plague variability. We propose that the PDO's impact on plague is conveyed via its effect on precipitation and temperature and the effect of precipitation and temperature on plague hosts and vectors: warmer and wetter climate leading to increased plague activity and thus an increased number of human cases. Our analysis furthermore provides insights into the consistency of plague mechanisms at larger scales.