An isatin-Schiff base ligand (ISS) bearing a pyridine-2-carboxamidine moiety was synthesized through a facile and convenient method for the highly selective colorimetric detection of Hg+ 2 and F− ions. The sensing ability of the synthesized ISS sensor toward Hg+ 2 and F− was established using colorimetric and UV–visible techniques. The developed sensor showed excellent selectivity in the presence of other competing ions for Hg+ 2 and F−, with a color change from yellow to red. The limits of the detection for sensing Hg+ 2 and F− were calculated to be 2.9× 1 0− 6 M and 1.4× 1 0− 5 M, respectively. Job’s plot based on spectroscopic data revealed a 1: 1 binding stoichiometry between ISS and Hg+ 2 or F− ion. Furthermore, the binding mechanism, optimized structures and electronic properties of ISS, ISS-F− adduct and ISS-Hg+ 2 complex were investigated using density functional theory (DFT) calculations. DFT results indicated a decrease of the HOMO–LUMO energy gap for ISS upon interaction with the F− and Hg+ 2 species which were in good agreement with the experimental outcomes.