<p>Derivatives of thiacalix[4]crown-ethers in <i>1</i>,<i>3-alternate</i> conformation with dodecyloxy and bromopropoxy groups were studied as ionophores for potentiometric sensor materials with plasticized polymeric membranes. The sensitivity of the sensors to alkaline, alkaline earth, and transition metal ions in aqueous solutions was investigated. It was revealed that the size of the crown ether macrocycle plays the main role in the sensitivity of sensors to metal ions, while the type of alkoxy group marginally affects this parameter. Sensors with thiacalix[4]arene-crown-5 exhibit selectivity for K⁺ ions. The developed sensors have shown high selectivity to Pb²⁺ ion in the presence of Ni²⁺, Co²⁺, Cu²⁺, Cd²⁺ ions and can be employed for selective Pb²⁺ quantification in aqueous media. The pH-sensitivity of sensors with bromopropoxy-substituted thiacalix[4]crown-ethers decreases with an increase in the crown cavity size, while that of dodecyloxy-substituted thiacalix[4]crown-ethers remains low regardless of the size of the crown cavity. Quantum-chemical calculations of the metal ion–thiacalixcrown-ether complex formation indicate ion–π interactions of Pb²⁺ and Cd²⁺ with benzene ring of thiacalix[4]arene and ion–dipole interactions with oxygen atoms of crown-ether, whereas alkali metal ion complexes (Na⁺, K⁺) are stabilized by ion–dipole interactions. The combined experimental and theoretical data suggest that the potentiometric selectivity of the thiacalix[4]crown-ethers in alkali and transition metal ion series is better interpreted as the interplay of metal ion desolvation and desolvated metal-ion complexation with macrocycle.</p>