Developing efficient methods for Mn separation is the most challenging in exploring innovative and sustainable acid mine drainage (AMD) treatments. The availability and capacity of certain waste materials for Mn removal warrant further exploration of their performance regarding the effect of process factors. This study addressed the influence of AMD chemistry (initial pH and concentrations of Mn, sulfate, and Fe), the solid/solution ratio, and the contact time on Mn separation by wood ash (WA) and bone char (BC). At an equivalent dose, WA displayed higher neutralization and Mn removal capacity over the initial pH range of 2.5–6.0 due to lime, dicalcium silicate, and fairchildite dissolution. On the other hand, at optimal doses, Mn separation by BC was faster, it was less affected by coexisting sulfate and Fe(II) species, and the carbonated hydroxyapatite structure of BC remained preserved. Efficient removal of Mn was feasible only at final pH values ≥ 9.0 in all systems with WA and at pH 6.0–6.4 using BC. These conclusions were confirmed by treating actual AMD with variable doses of both materials. The water-leaching potential of toxic elements from the AMD/BC treatment residue complied with the limits for inert waste. In contrast, the residue of AMD/WA treatment leached non-toxic quantities of Cr and substantial amounts of Al due to high residual alkalinity. To minimize the amount of secondary waste generated by BC application, its use emerges particularly beneficial after AMD neutralization in the finishing step intended for Mn removal.