This paper proposes a high-sensitivity U-shaped optical fiber sensor based on indium tin oxide (ITO) for surface plasmon resonance (SPR) sensing. Finite element simulations reveal that introducing ITO enhances the surface electric field strength by 1.15× compared to conventional designs, directly boosting sensitivity. The U-shaped structure optimizes evanescent wave–metal film interaction, further improving performance. In an external refractive index (RI) range of 1.334–1.374 RIU, the sensor achieves a sensitivity of 4333 nm/RIU (1.85× higher than traditional fiber sensors) and a figure of merit (FOM) of 21.7 RIU⁻¹ (1.68× improvement). Repeatability tests show a low relative standard deviation (RSD) of 0.4236% for RI measurements, with a maximum error of 0.00018 RIU, confirming excellent stability. The ITO coating’s strong adhesion ensures long-term reliability. With its simple structure, ease of fabrication, and superior sensitivity/FOM, this SPR sensor is well-suited for high-precision biochemical detection in intelligent sensing systems.