Selenium is a beneficial trace element for humans, animals, and plants, and adequate intake contributes to health, growth, and development. Selenium accumulation in sweet potato varies among genotypes. In this study, 77 sweet potato germplasm resources were planted in the Wuming natural selenium‑rich soil region and the Mingyang low‑selenium soil region. The differences and correlations in major agronomic traits, quality traits, and tuber selenium content between the two regions were analyzed, and natural selenium‑enriched germplasm were screened. The results showed that yield, vine length, branch number, and fresh vine and leaf weight per plant in the Mingyang low‑selenium region were higher than those in the Wuming selenium‑rich region, while storage root number per plant was similar between the two sites. Dry matter rate and total flavonoid content in Wuming were higher than those in Mingyang. Tuber selenium content in Wuming ranged from 0.034 to 0.319 mg/kg DW, with a mean of 0.070 mg/kg; in Mingyang, it ranged from 0.025 to 0.068 mg/kg DW, with a mean of 0.040 mg/kg. Zhenghong 163, Longzi 9, and Guangzishu 9 exhibited the highest selenium enrichment multiples and were identified as the optimal selenium‑enriched candidate varieties. Principal component analysis and cluster analysis further revealed the structural differences in trait variation between the two regions and the significant influence of soil selenium level on germplasm classification. This study provides core germplasm resources for selenium‑enriched sweet potato breeding and industrial development.