A highly selective and sensitive surface acoustic wave (SAW) sensor of dopamine (DA) was developed by depositing cobalt phthalocyanine (CoPc) nanopillars on gold-coated sensing platform of SAW sensor. The developed biosensor presents a sensitivity of 1.6°/nM, has a low limit of detection (LOD) on the order of 0.1 nM, and imparts more selectivity toward DA, since the detection limit of the interfering ascorbic acid (AA) is as high as 1 mM. To understand the selectivity mechanisms of this sensor toward DA, density functional theory-based chemical calculations were carried out. Calculations suggest two different types of interactions: dative bond with a very strong character for DA-CoPc complexes, and significant ionic character in the case of AA-CoPc ones. The interaction energies, in liquid phase, were estimated to be equal to -81 kJ mol(-1) and -38 kJ mol(-1) for DA-CoPc and AA-CoPc complexes, respectively, therefore accounting for the selective detection of DA over AA using tandem CoPc nanopillar-based SAW sensor device. This work demonstrates a simple and efficient design of SAW sensors employing thin nanostructured CoPc biomolecular recognition layers for DA detection.