The development of protective self-detoxifying materials is an important societal challenge to counteract risk of attacks employing highly toxic chemical warfare agents (CWAs). In this work, we have developed bifunctional zirconium metal-organic frameworks (MOFs) incorporating variable amounts of nucleophilic amino residues by means of formation of the mixed ligand [ZrO(OH)(bdc)(bdc-NH)] (UiO-66-xNH) and [ZrO(OH)(bpdc)(bpdc-(NH))] (UiO-67-x(NH)) systems where bdc = benzene-1,4-dicarboxylate; bdc-NH= benzene-2-amino-1,4-dicarboxylate; bpdc = 4,4'-biphenyldicarboxylate; bpdc-(NH) = 2,2'-diamino-4,4'-biphenyldicarboxylate and x = 0, 0.25, 0.5, 0.75, 1. In a second step, the UiO-66-xNH and UiO-67-x(NH) systems have been postsynthetically modified by introduction of highly basic lithium tert-butoxide (LiOBu) on the oxohydroxometallic clusters of the mixed ligand MOFs to yield UiO-66-xNH@LiOBu and UiO-67-x(NH)@LiOBu materials. The results show that the combination of pre and postsynthetic modifications on these MOF series gives rise to fine-tuning of the catalytic activity toward the hydrolytic degradation of both simulants and real CWAs in unbuffered aqueous solutions. Indeed, UiO-66-0.25NH@LiOBu is able to hydrolyze both CWAs simulants (diisopropylfluorophosphate (DIFP), 2-chloroethylethylsulfide (CEES), and real CWAs (soman (GD), sulfur mustard (HD)) quickly in aqueous solution. These results are related to a suitable combination of robustness, nucleophilicity, basicity, and accessibility to the porous framework.