There are two important factors, which are easily neglected, restricting the sensing performance of fiber-optic surface plasmon resonance (SPR) sensors. These are the selection of incident light modes and the uneven distribution of the sensing layer. In this paper, a fiber-optic SPR sensor model with a non-uniform sensing layer is first proposed. We use fiber-optic SPR sensor models with uniform and nonuniform sensing layers to study the impact of incident light modes and sensing layer non-uniformities on their sensing performances, respectively. In the case of a uniform sensing layer, the contributions of different single incident light modes are investigated and the optimal incident multimode form is selected as 1.41~π/2; the optimal thickness of the sensing layer is selected as 65 nm. In the case of a non-uniform sensing layer, the non-uniformity of the sensing layer has little effect on the sensing performances when the length of the sensing region is 10 mm. However, the length of the sensing region has an obvious effect on the sensing performances.