Two novel pyridine Schiff base derivatives, namely 3-pyridinecarboxaldehyde-4-phenyl thiosemicarbazide (3-PCPTC) and 4-pyridinecarboxaldehyde-4-phenylthiosemicarbazide (4-PCPTC), were synthesized and their corrosion inhibition properties on mild steel in 1.0 M HCl were studied through experimental and theoretical measurements. Weight loss, electrochemical impedance spectroscopy and potentiodynamic polarization results indicate that both compounds exhibit a good inhibition effect and that 3-PCPTC shows better inhibition efficiency than 4-PCPTC. Meanwhile, the adsorption process obeys the Langmuir adsorption isotherm model, and thermodynamic parameters were calculated and discussed. Scanning electron microscopy and X-ray photoelectron spectroscopy analyses confirm the adsorption and protective abilities of the two studied inhibitors on mild steel in HCl. UV-vis spectroscopic studies show that the corrosion inhibitors interact with mild steel in HCl solution to form Fe-inhibitor complexes. Furthermore, quantum chemical calculations and molecular dynamics simulations were performed. According to the experimental and theoretical results, the inhibition mechanism was deduced.