The establishment of pioneer plants in waste slag sites not only modifies the nutrient content of the waste, but also plays a significant role in regulating the pH and potentially toxic elements (PTEs), thereby providing favorable conditions for the quick introduction of other plants. However, the mechanisms by which pioneer plants impact the migration and transformation of PTEs in polymetallic mines have rarely been studied. In this study, we investigated the effects of pioneer phytoremediation on the migration and transformation of PTEs, specifically thallium (Tl), mercury (Hg), arsenic (As), and antimony (Sb), in mercury-thallium mine waste. The results showed that pioneer phytoremediation increased esters and ethers containing C-O and P-O groups in dissolved organic matter, which subsequently formed soluble complexes with Hg, As, and Sb. Nevertheless, pioneer phytoremediation reduced the migration of Tl in the waste, this was mainly because pioneer phytoremediation reduced Fe3+ in silicate minerals and iron-containing minerals to more reactive Fe2+, thereby increasing the electronegativity (El) of the waste and enhancing its adsorption capacity for metal cations, such as Hg and Tl, thus maintaining electrical neutrality. However, the increased El of the waste was detrimental to the adsorption of negatively charged oxygen-containing anions, such as As and Sb. At the same time, the dissolution of Fe2+ resulted in the release and mobility of As and Sb that had been adsorbed onto iron oxides. The results offer significant theoretical support for guiding the ecological restoration of PTEs in polymetallic mines.