Nanoscale CuO with diameters in the range of 7–8 nm has been synthesized via a two-step precipitation–calcination method using copper(II) isonicotinate tetrahydrate as the precursor. The first step involves the room temperature stirring of an alkaline ethanolic solution of the precursor which gives a non-crystalline CuO species, while the second step involves the calcination of the product of the first step at 180 °C to form nanocrystalline CuO which has been characterized by PXRD, TEM, SEM, H₂-TPR and Raman spectroscopy, etc. The CuO material has shown excellent catalytic activity in the oxidation of styrene using TBHP as the oxidizing agent leading to complete styrene conversion with more than 95% styrene oxide selectivity at the end of 6 h. The oxide catalyst can be reused for at least 6 successive runs without significant loss in activity.