The use of water–ethanol mixtures in hot pressurized liquid extraction (HPLE) to recover phenolic compounds from agro-industrial waste has been successfully investigated. However, the unresolved challenge of reducing solvent costs associated with the process hinders the scaling of this eco-friendly technology. This study evaluated the use of isopropanol as an alternative, lower-cost solvent for recovering polyphenols from discarded blueberries through the HPLE process. HPLE was carried out using water–isopropanol mixtures (0, 15 and 30%) at 70, 100, and 130 °C. The total polyphenol content (TPC), antioxidant capacity (DPPH and ORAC), glucose and fructose contents, and polyphenol profile of the extracts were determined. HPLE extracts obtained using high isopropanol concentrations (30%) and high temperatures (130 °C) presented the highest TPC (13.57 mg GAE/gdw) and antioxidant capacity (IC50: 9.97 mg/mL, ORAC: 246.47 µmol ET/gdw). Moreover, the use of 30% water–isopropanol resulted in higher yields of polyphenols and removal of reducing sugars compared to atmospheric extraction with water–acetone (60%). The polyphenolic profiles of the extracts showed that flavanols and phenolic acids were more soluble at high concentrations of isopropanol (30%). Contrarily, flavonols and stilbenes were better recovered with 15% isopropanol and pure water. Therefore, isopropanol could be a promising solvent for the selective recovery of different bioactive compounds from discarded blueberries and other agro-industrial residues.