Probably the simplest way is using subplot2grid, described in Customizing Location of Subplot Using GridSpec.
ax = plt.subplot2grid((2, 2), (0, 0))
is equal to
import matplotlib.gridspec as gridspec
gs = gridspec.GridSpec(2, 2)
ax = plt.subplot(gs[0, 0])
so bmu's example becomes:
import numpy as np
import matplotlib.pyplot as plt
# generate some data
x = np.arange(0, 10, 0.2)
y = np.sin(x)
# plot it
fig = plt.figure(figsize=(8, 6))
ax0 = plt.subplot2grid((1, 3), (0, 0), colspan=2)
ax0.plot(x, y)
ax1 = plt.subplot2grid((1, 3), (0, 2))
ax1.plot(y, x)
plt.tight_layout()
plt.savefig('grid_figure.pdf')