The hydrolysis of [RhCl6]3- in NaOH-water solutions was studied by spectrophotometric methods. The reaction proceeds via successive substitution of chloride with hydroxide to quantitatively form [Rh(OH)6]3-. Ligand substitution kinetics was studied in an aqueous 0.434-1.085 M NaOH matrix in the temperature range 5.5-15.3 °C. Transformation of [RhCl6]3- into [RhCl5(OH)]3- was found to be the rate-determining step with activation parameters of ΔH† = 105 ± 4 kJ mol-1 and ΔS†= 59 ± 10 J K-1 mol-1. The coordinated hydroxo ligand(s) induces rapid ligand substitution to form [Rh(OH)6]3-. By simulating ligand substitution as a dissociative mechanism, using density functional theory (DFT), we can now explain the relatively fast and slow kinetics of chloride substitution in basic and acidic matrices, respectively. Moreover, the DFT calculated activation energies corroborated experimental data that the kinetic stereochemical sequence of [RhCl6]3- hydrolysis in an acidic solution proceeds as [RhCl6]3- → [RhCl5(H2O)]2- → cis-[RhCl4(H2O)2]-. However, DFT calculations predict in a basic solution the trans route of substitution [RhCl6]3- → [RhCl5(OH)]3- → trans-[RhCl4(OH)2]3- is kinetically favored.