Oxidation of n‐butane to produce maleic anhydride (MA) by the vanadium phosphorus oxide (VPO) catalyst is important for the fine chemical industry. However, the improvement in MA yield exceeding 60% is still a big challenge. In this article, a VPO catalyst with increased MA yield originated from the tailored structure of VPO precursor prepared in a rotating packed bed (RPB) reactor with excellent micro‐mixing efficiency. The activated VPO‐RPB catalyst displayed the coexistence of X1‐VOPO4 and αI‐VOPO4 phases and enhanced reducibility of V4+ state. Remarkably, the MA yield in n‐butane oxidation catalyzed by VPO‐RPB reached up to 66%, showing an increment by 14% compared with VPO‐STR prepared in a stirring tank reactor (STR). The VPO‐RPB showed the repeatable catalytic performance and achieved a promising scale‐up production. This work provides the experimental evidence of a dual‐phase (X1‐VOPO4 and αI‐VOPO4) mechanism for n‐butane oxidation, and reveals the structure–activity dependence of VPO catalyst.