The aim of this study was to reach the best efficiency of total polyphenols extraction from beech bark. The impacts of solvent concentration, sonication time, and temperature were investigated relative to the yield of extractives from beech (Fagus sylvatica L.) bark using ultrasound-assisted extraction at 40 kHz ultrasonic frequency. All extracts were characterized quantitatively in terms of total content in polyphenols. The extracts obtained in the optimized conditions were also evaluated qualitatively. Beech bark can be a rich raw material for obtaining bioactive polyphenols. An experimental planning method was described that optimized the process and increased the extraction yield. In the experiments, water and ethanol:water solvent solutions were used. The efficiency of the extraction process was determined based on a factorial analysis of variance. The maximum extraction yield of total polyphenols (72.716 mg gallic acid equivalents/g beech bark) was obtained using a processing time of 20 min, an extraction temperature of 65 °C, and an ethanol solvent concentration of 70%. The extracts obtained under the optimum conditions were characterized to determine potential uses of beech bark extractives. The results obtained indicated that ultrasound-assisted extraction was an efficient method for the extraction of natural compounds from beech bark; thus, this method allows for the full utilization of this abundant and low-cost industrial waste.