The displacement of water molecule(s) from the inner coordination sphere of [Gd(DTTA–Me)(H2O)2]− (DTTA = ethylenetriamine-N,N,N″,N″-tetraacetate) by fluoride has been studied by multinuclear NMR relaxation (1H, 17O, 19F) and DFT calculations. Fluoride anions can replace only one of the coordinated water molecules. The thermodynamic stability constant (KGdLF,2980 = 11.6 ± 0.3) and thermodynamic parameters characterizing the formation of [Gd(DTTA–Me)(H2O)F]2– were determined (ΔH0 = +6.3 ± 0.1 kJ mol–1; ΔS0 = +41.5 ± 3.4 J mol–1 K–1; ΔV0 = +4.5 ± 1.2 cm3 mol–1). Fluoride binding causes a marked acceleration of the water exchange, which is seven times faster for [Gd(DTTA–Me)(H2O)F]2– (kex,1298 = 177 × 106 s–1) than for [Gd(DTTA–Me)(H2O)2]− (kex,2298 = 24.6 × 106 s–1). Water exchange on both compounds is faster than formation of the fluoride complex. The analysis of the Gd–Owater distances, electron density, and electron localization function (ELF) at the bond critical points using DFT calculations reveals that F– binding weakens the Gd–Owater bonds, thereby facilitating the departure of the coordinated water molecule following a dissociative mechanism. The water exchange on both Gd(DTTA–Me) complexes follow dissociative reaction pathways as shown by the positive activation volumes ΔV⧧ = +8 ± 2 cm3 mol–1 and +15 ± 4 cm3 mol–1 for the bis-aqua complex and the monofluoro complex, respectively.