Methane-oxidizing cultures from five different inocula were enriched to be used for co-metabolic degradation of micropollutants. In a first screening, 18 different compounds were tested for degradation with the cultures as well as with four pure methane-oxidizing bacterial (MOB) strains. The tested compounds included pharmaceuticals, chemical additives, pesticides, and their degradation products. All enriched cultures were successful in the degradation of at least four different pollutants, but the compounds degraded most often were sulfamethoxazole (SMX) and benzotriazole (BTZ). Addition of acetylene, a specific methane monooxygenase (MMO) inhibitor, revealed that SMX and BTZ were mainly degraded co-metabolically by the present MOB. The pure MOB cultures exhibited less degradation potential, while SMX and BTZ were also degraded by three of the four tested pure strains. For MOB, copper (Cu2+) concentration is often an important factor, as several species have the ability to express a soluble MMO (sMMO) if the Cu2+ concentration is low. In literature, this enzyme is often described to have a broader compound range for co-metabolic degradation of pollutants, in particular when it comes to aromatic structures. However, this study indicated that co-metabolic degradation of the aromatic compounds SMX and BTZ was possible at high Cu2+ concentration, most probably catalyzed by pMMO.