Ultrafast, polarization-selective time-resolved X-ray absorption near-edge structure (XANES) was used to characterize the photochemistry of vitamin B-12,, cyanocobalamin (CNCb1), in solution. Cobalamins are important biological cofactors involved in methyl transfer, radical rearrangement, and light-activated gene regulation, while also holding promise as light-activated agents for spatiotemporal controlled delivery of therapeutics. We introduce polarized femtosecond XANES, combined with UV-visible spectroscopy, to reveal sequential structural evolution of CNCbl in the excited electronic state. Femtosecond polarized XANES provides the crucial structural dynamics link between computed potential energy surfaces and optical transient absorption spectroscopy. Polarization selectivity can be used to uniquely identify electronic contributions and structural changes, even in isotropic samples when well-defined electronic transitions are excited. Our XANES measurements reveal that the structural changes upon photoexcitation occur mainly in the axial direction, where elongation of the axial Co-CN bond and Co-N-Im bond on a 110 fs time scale is followed by corrin ring relaxation on a 260 fs time scale. These observations expose features of the potential energy surfaces controlling cobalamin reactivity and deactivation.