Zinc-substituted hydroxyapatite samples with a preset degree of substitution (Са10 – хZnx(PO4)6(OH)2, x = 0.1–2.0) have been synthesized by a mechanochemical method. The composition of starting components ((Zn(H2PO4)2 ⋅ 2Н2О and ZnO) and water of crystallization have been shown to influence the apatite structure formation process and the degree of zinc substitution for calcium in the mechanochemical synthesis and annealing processes. When ZnO was used as a dopant, beta-tricalcium phosphate was observed to form as a reaction intermediate directly in the mill after 5–10 min of the reaction mixture milling and disappear after 20 min of milling. The final synthesis product—zinc-substituted hydroxyapatite—remains single-phase for x ≤ 0.8 in the case of Zn(H2PO4)2 ⋅ 2Н2О and x ≤ 0.25 in the case of ZnO. After annealing, the zinc-substituted hydroxyapatite is single-phase only in the case of zinc phosphate using at x ≤ 0.1.