In this study, biochars (BC) from potato peel residuals were synthesized at 400, 600, and 800 °C, characterized, and evaluated for the persulfate-assisted oxidation of venlafaxine (VEN). BC pyrolyzed at 800 °C demonstrated the highest catalytic activity, resulting in the degradation of 750 μg/L of VEN in the presence of 500 mg/L persulfate in less than 90 min. Acidic conditions favored VEN destruction, while the apparent kinetic constant was reduced from 0.1136 at pH 3 to 0.0389 and 0.0352 min−1 for pH 7 and 9, respectively. Interestingly, the presence of inorganic ions such as bicarbonates and chlorides, as well as humic acid, only slightly reduced process efficiency. Scavenging tests and electron paramagnetic resonance spectroscopy indicate a mixed mechanism dominated by non-radical pathways, with minor radical contributions, mediated by oxygenated surface functionalities of the 800 °C biochar. Five transformation products were identified through LC-HRMS suspect and non-target approaches, and a potential degradation pathway was proposed. Most of the identified transformation products exhibited lower toxicity levels than the parent compound. Finally, life cycle analysis revealed that, despite its superior kinetics, the 800 °C biochar carries the largest environmental footprint, underscoring the need for integrated assessments that jointly optimize removal performance and environmental impacts.