The size-dependent stiffness variations in nanocrystalline anatase, a leading material for applications in photovoltaics, photocatalysis, photoelectrochromics, sensors, and optical coatings, were determined using in situ synchrotron x-ray diffraction and Raman scattering. An unusual, abrupt change in the compression curve at approximately 10 GPa and subtle breaks in the pressure shifts of the intense E(g) Raman band at approximately 10 and approximately 15 GPa have been correlated with approximately 2 A-scale disordering of nanocrystalline anatase structure that fully amorphizes under high compression.