The Guitar nebula is a spectacular example of an H-alpha bow shock nebula produced by the interaction of a neutron star with its environment. The radio pulsar B2224+65 is traveling at ~800--1600 km/s (for a distance of 1--2 kpc), placing it on the high-velocity tail of the pulsar velocity distribution. Here we report time evolution in the shape of the Guitar nebula, the first such observations for a bow shock nebula, as seen in H-alpha imaging with the Hubble Space Telescope. The morphology of the nebula provides no evidence for anisotropy in the pulsar wind, nor for fluctuations in the pulsar wind luminosity. The nebula shows morphological changes over two epochs spaced by seven years that imply the existence of significant gradients and inhomogeneities in the ambient interstellar medium. These observations offer astrophysically unique, in situ probes of length scales between 5E-4 pc and 0.012 pc. Model fitting suggests that the nebula axis -- and thus the three-dimensional velocity vector -- lies within 20 degrees of the plane of the sky, and also jointly constrains the distance to the neutron star and the ambient density.