I want to make a matplotlib figure that has two components:  A 2x2 "four pack" of subplots in the lower half of the figure  A subplot above the four pack that is the size of the four pack.   I have seen this answer where subplots can have different dimensions. How can that approach be tweaked when there are multiple columns and rows, however? Or is a completely different approach warranted? My final figure should be arranged something like this:  If there is a straightforward way to have a left-right oritentation, shown below, that would be helpful, too. 
You can use plt.subplot_mosaic or GridSpec. Someone else can write an answer using GridSpec, but here is how you'd do it using subplot_mosaic. For the large plot on top and 4 below it: import matplotlib.pyplot as plt fig, axs_dict = plt.subplot_mosaic("AA;AA;BC;DE")  If you want to put the large plot on the left and the four smaller on the right then just using this string: "AABC;AADE".