This study aimed to optimize pressurized liquid extraction (PLE) of phenolic compounds from the brown seaweed Fucus vesiculosus to obtain extract with high yield, rich in phenolic compounds, with good radical scavenging, and with metal chelating ability. The extraction was optimized with a Box–Behnken design experiment and response surface tool. Optimal condition was found at 137.18 °C, 58.65% v/v ethanol in water and 4.68 min extraction time which resulted in yield of 31.16% dry basis, total phenolic content (TPC) of 3.69 g gallic acid equivalent (100 g dry seaweed)−1, effective concentration for 50% inhibition (EC50) of DPPH radical (92.6 μg mL−1), ABTS radical (2.35 mg mL−1), and metal chelating (1.10 mg mL−1). The TPC value and radical scavenging activity of the PLE extract were insignificantly different from the one obtained from conventional solvent extraction, which proved PLE advantages in terms of shorter time and less solvent requirement. Gallic, protocatechuic, and gentisic acids were identified in the PLE extracts.