The Bajío—Mexico’s central lowlands—is a region of economic importance because of its agricultural industry. Over time, agricultural practices have led to soil deterioration, loss of fertility, and abandonment. In this study, six agricultural soils were analyzed: AGQ, CTH, CTJ, JRM, CRC, and CYI, and used to develop a soil quality index (SQI) that includes the use of physicochemical, biological, and ecophysiological indicators to differentiate soil quality. Principal component analysis (PCA) was used, reducing the indicators from 46 to 4, which represents 80.4% of data variability. It was implemented the equation of additive weights using the variance of the principal components as a weight factor for the SQI. The developed SQI was according to the indicators WHC, SLT, N-NO3−, and qCO2, differentiating the quality of soils from the agricultural management in low quality (JRM < CYI < AGQ) and moderate quality (CTJ < CRC < CTH). The use of biological and ecophysiological indicators added to the PCA and the equation of additive weights allowed establishing an SQI with a minimum of indicators, sensitive to agricultural management, facilitating its interpretation and implementation for the Mexican Bajío region and soils in similar conditions around the world.