<p>The development of efficient and mechanistically well-understood organic inhibitors for copper protection in strongly acidic environments remains a critical challenge for industrial corrosion control. In this work, three structurally related pyrano[2,3-c]pyrazole derivatives bearing electron-donating (–OCH₃), neutral (–H), and electron-withdrawing (–Cl) substituents, namely 6-amino-4-(4-methoxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (AMMC), 6-amino-3-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (AMPC), and 6-amino-4-(4-chlorophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (AMCC) were systematically investigated as corrosion inhibitors for copper in 0.5 M H₂SO₄. Electrochemical impedance spectroscopy and potentiodynamic polarization measurements revealed outstanding inhibition efficiencies exceeding 95% at 1.0 mM, with AMMC exhibiting the highest performance. Adsorption followed the Langmuir isotherm, and negative Gibbs free energies confirmed a spontaneous mixed adsorption mechanism with a dominant chemisorption contribution. SEM and AFM analyses showed the formation of compact and homogeneous protective films, leading to a pronounced reduction in surface roughness compared with uninhibited copper. Density functional theory calculations clarified substituent-induced electronic effects, showing that AMMC has the smallest energy gap, the highest softness, and the most favorable donor–acceptor balance. Molecular dynamics simulations, explicitly accounting for water and sulfate species, confirmed stable quasi-planar adsorption geometries and strong interaction energies on the Cu(111) surface. Overall, the combined electrochemical, surface-analytical, and atomistic results establish clear structure–property–performance relationships and provide mechanistic guidance for the rational design of high-efficiency, environmentally compatible copper corrosion inhibitors for acidic industrial applications.</p>