The olive alperujo (OA) corresponds to the solid waste generated in the olive oil extraction process using the two-phase centrifugation method. OA is produced in large quantities (800 kg OA/ton olives processed) and is characterized by its high moisture content, organic matter, and low pH. In Chile, the olive oil industry is recent, and one of its main challenges is to be able to manage OA to reduce the impact caused by its disposal. In this sense, its valorization as biogas by means of anaerobic digestion is an economically attractive option. For this, it is previously necessary to evaluate the biomethane potential (BMP) of the raw OA using batch assays. This study was focused on evaluating the factors that most affect the methane yield (MY) when using OA as substrate in BMP tests. First, a sweep analysis (Plackett–Burman) was applied to determine those factors that, according to the literature, would have an influence on the BMP tests. Among the factors studied, the most significant were preincubation, OA concentration, and agitation level. Subsequently, a 23 factorial experimental design was applied to evaluate the effect of these factors on MY at different levels. Results show that the OA concentration was the most significant factor affecting MY.