We used density functional theory to study the mechanism of n-butane oxidation to maleic anhydride on the vanadium phosphorus oxide (VPO) surface. We found that O(1)=P on the (VOPO4)-O-V surface is the active center for initiating the VPO chemistry through extraction of H from alkane C-H bonds. This contrasts sharply with previous suggestions that the active center is either the V-O bonds or else a chemisorbed O-2 on the ((VO)-O-IV)(2)P2O7 surface. The ability of O(1)=P to cleave alkane C-H bonds is due to its strong basicity coupled with large reduction potentials of nearby V-V ions. We examined several pathways for the subsequent functionalization of n-butane to maleic anhydride and found that the overall barrier does not exceed 21.7 kcal/mol.