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The effects of drought, a devastating natural disaster, have expanded due to intense global warming. Therefore, studying the spatio-temporal evolution and formation mechanism of drought is urgent and important. In this paper, the standardized precipitation evapotranspiration index (SPEI) of the source region of Yellow River was calculated for the years 1961-2015, and the heuristic segmentation and Modified Mann-Kendall methods were used to study the change points and trends of precipitation, temperature, and SPEI. The empirical orthogonal function was used to study the major modes of the SPEI, and cross wavelet analysis was used to demonstrate the relationship between SPEI and large-scale climate factors. The results initially demonstrated no change point and an insignificant positive trend in precipitation. Temperature revealed a significant increasing trend, and a change point was detected in 1997. SPEI indicated a change point in 1993, and a significant increasing trend was observed thereafter. These findings reveal that drought in the study area is highly related to the El Nino-Southern Oscillation. The North Atlantic and Arctic oscillations caused similar impacts on drought. By comparison, changes in SPEI were slightly related to the Pacific decadal oscillation. These results provide useful information for evaluating drought changes in the study area, early warning of drought, and water resource management.