The catalytic chloroacetylation of phenol and methoxyphenols was systematically investigated under identical conditions using ferric chloride (FeCl₃) and ferric chloride hexahydrate (FeCl₃·6H₂O) as Lewis acid catalysts. The study aimed to elucidate the effect of catalyst hydration state on reactivity, regioselectivity, and product distribution. Experimental results demonstrated that both catalysts efficiently promoted the reaction of phenol and its methoxy-substituted derivatives with chloroacetyl chloride. However, significant differences in selectivity were observed: FeCl₃ tended to favor O-acylation pathways, yielding chloroacetates as the main products, whereas FeCl₃·6H₂O exhibited higher activity toward C-acylation, leading to hydroxyphenacyl chloride derivatives. These differences were attributed to the varying coordination environments and catalytic behavior arising from the hydration state of the iron center. Spectroscopic analysis (IR, UV–Vis, and NMR) confirmed the structures of the obtained compounds and provided insight into the mechanism of electrophilic substitution. The comparative study revealed that methoxy substitution patterns strongly influenced the orientation of chloroacetylation, with ortho- and para-methoxy groups enhancing regioselectivity due to resonance and inductive effects. The findings highlight the role of catalyst hydration in controlling selectivity and suggest practical routes for tailoring chloroacetylated aromatic derivatives with potential applications in pharmaceuticals and fine chemicals. This work contributes to a deeper mechanistic understanding of chloroacetylation processes and provides a foundation for future research in selective functionalization of phenolic compounds under environmentally benign catalytic conditions.