Olive pomace is a waste produced by the olive oil industry in massive quantities each year. Disposal of olive pomace is difficult due to high concentrations of phenolic compounds, which is an environmental concern. However, phenolic compounds have applications in the health industry. Therefore, extraction of phenolic compounds from olive pomace has the potential to remove an environmentally hazardous portion of pomace while creating an additional source of income for farmers and producers. Using advanced technologies including Ultrasound Assisted Extraction (UAE), combined with water as an extraction solvent, has recently gained popularity. The present study outlines the optimal UAE conditions for the extraction of phenolic compounds with high antioxidant activity from olive pomace. Optimal conditions were developed using RSM for parameters power, time and sample-to-solvent ratio. Total phenolic compounds determined by Folin Ciocalteu method and total major bioactive compounds determined by HPLC as well as antioxidant capacity (DPPH and CUPRAC) were investigated. The optimal conditions for the extraction of phenolic compounds with high antioxidant activity were 2 g of dried pomace/100 mL of water at 250 W power for 75 min. UAE improved the extraction efficiency of water and yielded extracts with high levels of phenolic compounds and strong antioxidant activity.