Anaerobic digestion (AD) has been recently highlighted as the most efficient approach to manage vinasse in sugarcane biorefineries, providing both a renewable energy source (biogas) and a mineralized and nutrient-rich effluent suitable for agricultural use. However, the high sulfate concentrations (ca. 2 g L−1) present in vinasse and its seasonal availability (7–8 months) hinder the maximization of methane production in AD plants. This study investigated the use of sulfate-free vinasse (season) and molasses (off season), both pre-fermented in fermentative-sulfidogenic systems, as substrates to obtain enhanced year-round methane production in sugarcane biorefineries. Two second stage methanogenic structured-bed reactors operated at different temperatures (30 °C and 55 °C) were subjected to increasing organic loading rate (OLR) levels (1.0–20.0 kg COD m−3 d−1) in an experimental simulation of sequential periods of season, off season and season. An efficient start-up strategy enabled achieving operating stability in the full load project (10.0 kg COD m−3 d−1) in 37 d, which means anticipating the maximization of bioenergy production. Pre-fermenting vinasse and molasses was imperative for maintaining efficient organic matter conversion (80–90 %) into methane, regardless of the significant differences in lactate and phenols availability. A methane content in biogas ≥ 80 % and methane yield ≥ 330 NmL CH4 g−1COD were observed in both reactors, with no apparent observation of organic overloads. The results point towards a highly efficient strategy to maintain year-round high-rate biogas production from sugarcane vinasse, although the relatively high molasses demands can trigger an internal competition (with ethanol production) for substrate.