Cowpea (Vigna unguiculata L.) pods are an underexploited by-product of legume production with significant antioxidant potential. Their recovery and characterization support sustainable waste valorization in agri-food systems. This study aimed to optimize the extraction of phenolic compounds (PCs) with antioxidant capacity (AOC) from cowpea pods and identify key bioactives through experimental and theoretical approaches. First, high-intensity ultrasound extraction was optimized using response surface methodology with ethanol–water mixtures. Under optimal conditions (20% amplitude, 15 min, 50% ethanol), the ethanolic extract (Eo) showed higher total phenolic content (TPC) and AOC than the aqueous extract (Wo). Subsequently, fractionation by Sephadex LH-20 chromatography yielded fractions E2 and W2 with enhanced TPC and AOC. Phytochemical profiling showed that E2 was enriched in caftaric acid, p-coumaric acid, and morin, while W2 had higher levels of caftaric, p-coumaric, and caffeic acids. Finally, density functional theory was used to assess thermodynamic parameters linked to antioxidant mechanisms (HAT, SET-PT, SPLET), revealing morin as the most effective radical scavenger, followed by caffeic and caftaric acids. These findings show that AOC depends not only on phenolic concentration but also on molecular structure and solvent interactions. Thus, cowpea pod extracts and fractions hold promise for antioxidant-rich formulations in food, nutraceutical, or cosmetic applications.