The bioaccumulation of selenium (Se) and heavy metals (HMs) in plants is important because it can affect plant health and human nutrition. Recognizing the factors affecting Se accumulation in plants may have important implications for agricultural practices and human health in selenium-rich regions. The study primarily focused on the interactions between Se and HMs in the soil–plant system of the Lower Dniester Valley. Total concentrations of HMs (Cu, Mn, Zn) were determined by atomic absorption spectrometry, while Se concentrations were determined by a sensitive single-test-tube fluorometric method in solutions and extracts. Water-soluble Se (0.09 ± 0.03 mg·kg−1) in soils was 32.1% of the total Se (0.33 ± 0.13 mg·kg−1) and increased with the total rising Se content (r = 0.845). The results indicated that plants had a greater Zn accumulation capacity than that of the other HMs, suggesting its importance as a trace element for plant requirements. Se also had a high bioaccumulation rate. Se and Zn accumulation varied in different soil types, reflecting differences in bioavailability. In contrast, Mn and Cu showed low bioaccumulation, which varied with soil conditions and anthropogenic Cu pollution. Despite the Cu contamination of the soils in the investigated region, it can be inferred that the hydrogeochemical province with high Se content in groundwater has favorable conditions for Se mobilization in soils. The absence of antagonistic interactions with HMs in the soil–plant system contributes to the enhanced Se accumulation in plants in the Lower Dniester Valley. These results emphasize the complexity of the interactions between Se and HMs in the soil–plant system and their potential impact on agricultural practices.