A novel refractive index (RI) sensor based on a D-shaped single-mode-graded-index multimode-single-mode fiber (D-SGIMS) structure is presented and investigated in detail. A CO2 laser was used to process the SGIMS structure, which produced a strong evanescent field. The structural parameters were determined via simulations, and the experimental results were consistent with those of the theoretical analysis. The transmission spectra and RI sensitivity of the fabricated sensors with different lengths were compared via experiments, the results of which indicated that the maximum RI sensitivity was 811.00 nm/RIU in the range 1.333–1.419. Therefore, the proposed D-SGIMS structure can provide high-precision measurement capabilities and can be applied in the field of biochemistry. [ABSTRACT FROM AUTHOR]