This study aimed at analyzing the anaerobic co-digestion of microalgal biomass grown in wastewater and wheat straw. To this end, Biochemical Methane Potential (BMP) tests were carried out testing different substrate proportions (20–80, 50–50 and 80–20%, on a volatile solid basis). In order to improve their biodegradability, the co-digestion of both substrates was also evaluated after applying a thermo-alkaline pretreatment (10% CaO at 75 °C for 24 h). The highest synergies in degradation rates were observed by adding at least 50% of wheat straw. Therefore, the co-digestion of 50% microalgae – 50% wheat straw was investigated in mesophilic lab-scale reactors. The results showed that the methane yield was increased by 77% with the co-digestion as compared to microalgae mono-digestion, while the pretreatment only increased the methane yield by 15% compared to the untreated mixture. Thus, the anaerobic co-digestion of microalgae and wheat straw was successful even without applying a thermo-alkaline pretreatment.