Seaweed, in particular, brown seaweed, has gained research interest in the past few years due to its distinctive phenolic profile that has a multitude of bioactive properties. In order to obtain the maximum extraction efficiency of brown seaweed phenolic compounds, Response Surface Methodology was utilized to optimize the ultrasound-assisted extraction (UAE) conditions such as the amplitude, time, solvent:solid ratio, and NaOH concentration. Under optimal conditions, UAE had a higher extraction efficiency of free and bound phenolic compounds compared to conventional extraction (stirred 16 h at 4 °C). This led to higher antioxidant activity in the seaweed extract obtained under UAE conditions. The profiling of phenolic compounds using LC-ESI-QTOF-MS/MS identified a total of 25 phenolics with more phenolics extracted from the free phenolic extraction compared to the bound phenolic extracts. Among them, peonidin 3-O-diglucodise-5-O-glucoside and hesperidin 5,7-O-diglucuronide are unique compounds that were identified in P. comosa, E. radiata and D. potatorum, which are not reported in plants. Overall, our findings provided optimal phenolic extraction from brown seaweed for research into employing brown seaweed as a functional food.