Soil salinization seriously threatens agricultural production and ecological environments in arid areas. The accurate and rapid monitoring of soil salinity and its spatial variability is of great significance for the amelioration of saline soils. In this study, 191 soil samples were collected from cotton fields in southern Xinjiang, China, to obtain spectral reflectance and electrical conductivity (EC) indoors. Then, multi-granularity spectral segmentation (MGSS) and seven conventional spectral preprocessing methods were employed to preprocess the spectral data, followed by the construction of partial least squares regression (PLSR) models for soil EC estimation. Finally, the performance of the models was compared. The results showed that compared with conventional spectral preprocessing methods, MGSS could greatly improve the correlation between spectrum and soil EC, extract the weak spectral information of soil EC, and expand the spectral utilization range. The model validation results showed that the PLSR model based on the second-order derivative (2nd-der-PLSR) had the highest estimation accuracy among the models constructed by conventional methods. However, the PLSR model based on MGSS (MGSS-PLSR) had the highest estimation accuracy among all models, with Rp2 (0.901) and RPD (3.080) being 0.151 and 1.302 higher than those of the 2nd-der-PLSR model, respectively, and nRMSEP (5.857%) being 4.29% lower than that of the 2nd-der-PLSR model. The reason for the high accuracy of the MGSS-PLSR model is as follows: In the continuous segmentation of the raw spectrum by MGSS, the bands with strong and weak correlations with respect to soil EC were concentrated during low granularity segmentation. With the increase in granularity level, the spectral features decreased and were distributed discretely. In addition, the locations of spectral features were also different at different granularity levels. Therefore, the spectral features of soil EC can be effectively extracted by the MGSS, which significantly improves the spectral estimation accuracy of soil salinity. This study provides a new technical means for soil salinity estimation in arid areas.