Busia Gold mines in eastern Uganda generate significant wastes that contribute to environmental and health challenges in the region. This study assessed the extent of 9 potentially toxic metals (PTMs) present in Busia gold mine tailings. The study also evaluated environmental risks for each of the PTMs, using contamination indices. The indices were: index of geo accumulation (Igeo); potential ecological risk index (RI); contamination factor (CF); pollution load index (PLI) and ecological risk factor (ERI). Tailing samples were collected at two distinct depths; surface (0–30 cm) and deep (30–60 cm) from four sites. The samples were analyzed using an Atomic Absorption Spectrometry (AAS). The Igeo results showed that As and Hg recorded extreme pollution levels (Igeo >5) in all 4 sites. The other seven PTMs in all the sites were classified between heavily polluted to unpolluted categories. CF results revealed extreme contamination for Hg at site-A and As at site-M with moderate contamination of Ni, Zn, and Co at sites-C and B. RI findings showed that all the sites recorded RI > 600, with the highest (RI = 80, 407) at site-A, followed by site-C (RI = 74, 536). All the sites had a high level of ecological impact with greater potential for environmental risks in the area. In the case of PLI, all the sites were classified as polluted sites (PLI > 1). Sites-M and C recorded the highest (PLI = 12), followed by sites-B and A, with PLIs of 11 and 9, respectively. ERI findings for all the sites showed significant Hg, As, and Cd contamination, (ERI >320). Site-A recorded the highest Hg contamination (ERI = 78, 825). Site-M recorded elevated levels of As and Cd, with ERI of 1, 323, and 399, respectively. Pb at site-M posed considerable potential ecological risk with an ERI of 108, while Zn, Cu, Co, Ni, and Cr presented low ecological risk across all sites with ERI˂ 40. There is, therefore, need to properly manage tailings in Busia gold fields to minimize ecological contamination to avoid impacts on human, animal, and plant health.