The Great Lakes Basin is an important agricultural region for both the United States and Canada. The regional crop growths are affected by inter-annual climatic conditions and intra-seasonal variability. Consequently, monthly climate change projection data can provide more useful information for crop management than seasonal climate projections. However, very few studies undertaken for the Great Lakes Basin have focused on monthly timescales. In this study, we investigate the projected mid-century (2030–2059) monthly mean maximum temperature (Tmax) and minimum temperature changes of this region, relative to the baseline period (1980–2009). Future Tmax increases in this region are likely to be greater during the May to October period (coinciding with the region's growing season) than in other months. The order of magnitude of future Tmax and Tmin changes of the five Great Lakes sub-basins are Superior > Huron > Michigan > Erie and Ontario. Most future Tmax changes over land areas are higher than those over the lakes, whereas Tmin changes are likely to be higher over lakes than over the adjacent land areas in this region. The future number of extreme warm days (Tmax ≥ 29–32 °C) in this region will increase by between about 5 days (in the north) to 40 days (in southern parts of the basin), while the number of winter cold days (Tmax ≤ −5 °C ˜ 0 °C) may decrease by between 3 days (south) and 35 days (north). This study furthermore identifies some fluctuations of latitudinal temperature gradients in the Great Lakes Basin, these areas covering the north latitude 40.5–41.5°, 43.5–44.0°, 45.5–46.5°, and 47.5–49.5°.