A fiber-optic surface plasmon resonance (SPR) sensor for the detection of human blood groups is proposed. Previous experimental results describing the wavelength-dependent refractive index variation of multiple samples of different blood groups are considered for theoretical calculations. The spectral interrogation method, along with silica fiber and silver layer, is considered. The sensor’s performance is closely analyzed in terms of shift in SPR wavelength and SPR curve width in order to optimize the design parameters for a reliable and accurate blood-group identifier. The sensor design parameters include silver layer thickness, fiber core diameter, sensing region length, and temperature variation. The results are explained in terms of light coupling and plasmon resonance condition. The proposed sensing probe is able to provide high sensitivity and accuracy of blood-group detection, thereby opening an easy and reliable window for medical applications.