To understand the formation mechanism and evolution process of the perpendicular cavitation vortex (PCV) of an axial flow pump for off-design conditions, turbulent cavitating flows were numerically investigated using the rotation curvature-corrected shear stress transport (SST-CC) turbulence model and the Zwart–Gerber–Belamri cavitation model. In this work, the origin and evolution of a PCV were analyzed through a high-speed photography experiment and numerical simulation. The results showed that the PCV came from a secondary tip leakage vortex (S-TLV) and was aggregated by the action of the re-entrant jet, combined with the cavitation bubbles driven by the radial flow to form the cavitation vortex (CV). With the joint action of leakage jet lifting and TLV entrainment, the PCV was reoriented and gradually became perpendicular to the chord direction. Then, the PCV and TLV collided, mixed, and entrained, which formed a strong pressure pulsation. The PCV was gradually divided into upper and lower parts. One part was combined with the residual part of the TLV and flowed to the next blade, and the other part flowed out of the impeller area along the axial direction. At the same time, the generation, evolution, and dissipation of the PCV formed high pulsation amplitudes and frequencies in the middle and rear above the blade suction.