Mercury (Hg) is a highly toxic contaminant posing serious ecological and human health risks. This study investigates the Hg transfer characteristics and prediction models in a soil–lettuce system, employing bioconcentration factors (BCF), path analysis (PA), and Freundlich-type functions. A pot experiment was conducted in a greenhouse, where lettuce was grown in a range of Chinese agricultural soils (n = 21) and deliberately spiked with Hg using Hg(NO₃)₂ solution. The results indicated that lettuce grown in Hg-spiked acidic soils (pH < 6.5) accumulated total Hg (THg) levels up to 14.01 µg kg⁻¹, surpassing the safe consumption limit of 10 µg kg⁻¹. The BCF for lettuce THg was less than 1.0, suggesting a low transfer of Hg from soil to lettuce. Notably, BCF values were significantly higher in acidic soils (0.02) compared to alkaline soils (0.005). Path analysis accounted for 82% of the variation in lettuce THg content, identifying soil THg, pH, and amorphous (Amo) Al and Fe oxides as primary direct factors. Additionally, soil-available Hg (AvHg), exchangeable Hg (ExHg), clay, and organic matter (OM) were significant indirect factors affecting lettuce THg content. To validate the findings of the path analysis, an extended Freundlich-type equation was developed using stepwise multiple linear regression (SMLR). This model exhibited high predictive accuracy (R² = 0.82, p ≤ 0.001), with soil pH, THg, and amorphous Al and Fe oxides being the key variables for predicting Hg transfer in the soil–lettuce system. The insights from this study can guide the management of safe lettuce production in Hg-contaminated soils, ensuring the mitigation of Hg exposure through agricultural produce.