In this study, temporal and spatial variability of ice cover in the Great Lakes are investigated using historical satellite measurements from 1973 to 2010. The seasonal cycle of ice cover was constructed for all the lakes, including Lake St. Clair. A unique feature found in the seasonal cycle is that the standard deviations (i.e., variability) of ice cover are larger than the climatological means for each lake. This indicates that Great Lakes ice cover experiences large variability in response to predominant natural climate forcing and has poor predictability. Spectral analysis shows that lake ice has both quasi-decadal and interannual periodicities of ~8 and ~4 yr. There was a significant downward trend in ice coverage from 1973 to the present for all of the lakes, with Lake Ontario having the largest, and Lakes Erie and St. Clair having the smallest. The translated total loss in lake ice over the entire 38-yr record varies from 37% in Lake St. Clair (least) to 88% in Lake Ontario (most). The total loss for overall Great Lakes ice coverage is 71%, while Lake Superior places second with a 79% loss. An empirical orthogonal function analysis indicates that a major response of ice cover to atmospheric forcing is in phase in all six lakes, accounting for 80.8% of the total variance. The second mode shows an out-of-phase spatial variability between the upper and lower lakes, accounting for 10.7% of the total variance. The regression of the first EOF-mode time series to sea level pressure, surface air temperature, and surface wind shows that lake ice mainly responds to the combined Arctic Oscillation and El Niño–Southern Oscillation patterns.