The distinct stages of anaerobic digestion (AD) exhibit varying effects on the removal of diverse organic micropollutants present in wastewater. This study demonstrates the effectiveness of AD phase separation (acidogenesis and methanogenesis) in a two-stage anaerobic fixed-film bioreactor in the removal of pharmaceuticals and personal care products (PPCPs) from wastewater. The acidogenic−-methanogenic reactor achieved removal rates of over 95% for the chemicals sulfamethoxazole, methylparaben, propylparaben, naproxen, and acetaminophen and surpassed the single-stage methanogenic reactor in the removal of the more persistent compounds, ibuprofen, carbamazepine, metoprolol, ciprofloxacin, and diclofenac. The acidogenic step played a pivotal role in degrading persistent PPCPs, likely attributed to the selection of microbial enzymes involved in the production of volatile fatty acids from the oxidation of carbohydrates. The key candidate microbial genera for the PPCPs biodegradation were identified in the acidogenic reactor as Bacteroides, Clostridium, Williamwhitmania, Catenisphaera, and Erysipelothrix. In the methanogenic reactor, there was a predominance of Rectinema, Smithella, Syntrophus, and Syntrophorhabdus in coculture with hydrogen-using methanogens (Methanoregula and Methanolinea). This innovative two-stage reactor presents a promising solution for efficient organic micropollutant elimination in wastewater treatment plants.