Eucalyptus robusta (E. robusta) has a significant value in traditional medicine and recently has been shown to possess many pharmacological properties in vitro. This study was designed to utilise microwave-assisted extraction (MAE) to yield optimal total phenolic content (TPC), total flavonoid content (TFC), proanthocyanidin levels and antioxidant capacity from E. robusta using water as the solvent, facilitated by the use of response surface methodology (RSM). A three-level-three-factor Box–Behnken design was implemented to elucidate the effect of irradiation time, power and sample-to-solvent ratio on the yields of these phytochemicals. The results highlighted the accuracy and reliability of RSM as a tool for predicting the yields of TPC, TFC, proanthocyanidins and total antioxidants using MAE. Sample-to-solvent ratio had the greatest impact on the TPC yield followed by power and irradiation time. The optimal MAE conditions for TPC and TFC were 3 min, 600 W power and 2 g/100 mL sample-to-solvent ratio. The experimental yield of TPC was 58.40 ± 1.03 mg GAE/g, and 19.15 ± 1.06 mg RE/g of TFC was obtained under these optimal conditions. These conditions, optimised for maximum TPC yield also liberated 62%, 64.6%, 66.3% and 67% of the maximum proanthocyanidins, ABTS, DPPH and CUPRAC values, respectively. This study revealed that MAE is a reliable and efficient method for extracting high yields of phytochemicals from E. robusta, with significant potential to be up-scaled for industrial, nutraceutical or pharmaceutical applications.