A surfactant-free, low temperature hydrothermal synthesis of Cu2O nanostructures is demonstrated for application to the photocatalytic degradation of trimethoprim (TMP), an environmental xenobiotic. Photophysical properties of different size and shape Cu2O nanostructures were determined by bulk and surface microscopic and spectroscopic analyses. Visible light photoactivity for the oxidative degradation of TMP is sensitive to the rate of photoexcited charge carrier bulk recombination, and therefore the size of Cu2O crystallites. Optimum photodegradation activity was observed for a hierarchical Cu2O nanostructure, comprising 11 nm crystallites nucleated as 50−80 nm particles, themselves coalesced into 400 nm compact agglomerates. The specific activity of 1.12 μmol.g−1. min−1 for a 0.1 mM TMP aqueous solution is comparable to previous reports that required higher energy and/intensity UV irradiation. The stepwise hydroxylation and oxidative cleavage of TMP to form monocylic fragments is driven by hydroxyl radicals photogenerated over the hierarchical Cu2O nanostructure, which exhibits excellent catalytic stability for >25 h.