In this study a variety of novel symmetrically and asymmetrically functionalized pillar[5]arenes were synthesized, structurally characterized and applied as ionophores in PVC-plasticized membrane potentiometric sensors. During the sensitivity studies it was found that these novel sensors demonstrate pronounced cationic response towards different metal ions in aqueous solutions. A selectivity evaluation revealed that the developed sensors do not possess sharp preferences to particular ions, but offer a broad cross-sensitivity and can be employed in potentiometric multisensor systems.