This paper proposed a simplified modeling approach for a power quality (PQ) assessment of Electric Submersible Pumps (ESP) systems supplied by the two-level, the neutral-point-clamped three-level, and the cascaded H-bridge (CHB) multilevel inverter VFD topologies. The VFD switching function models and their analytical expressions are proposed to understand how they can create high-frequency components that might excite the resonance mode in a transmission cable or a rotating shaft system. Voltage, current, and motor airgap torque harmonics induced by each VFD topology in a balanced operation mode are derived and correlated to the PWM carrier and motor operating frequencies. The motor airgap harmonics are calculated based on Concordia’s transformation of voltages and currents in αβ-plan. These harmonic components are represented in the form of Campbell diagrams. An analysis of harmonics under unbalanced conditions was also conducted in a CHB VFD topology-powered ESP system with failed and bypassed cells. The investigated modulation technique is a neutral-shift PWM method that enables the system to operate balanced line-line voltages even if the line-neutral voltages are unbalanced. The effects of modifying the electrical spectrum using the neutral-shift PWM method on electrical and mechanical spectra are analyzed. The results of the Matlab/Simulink-based simulation show that the proposed full ESP system model is highly accurate in both normal and failure modes. The results are consistent with theoretical predictions and are graphically shown in the time and frequency domains for easy analysis. Hybrid experimental–numerical results on a reduced-scale laboratory setup are also discussed to confirm the correctness of the suggested developments.