During the last few decades, the anaerobic digestion (AD) process has become a worldwide topic of interest since it is considered as one of the most suitable and cost-effective technologies to address the problem of wastewater treatment while generating bioenergy. Until today, the use of seawater in the operations of anaerobic digestion processes for biogas production was unfamiliar to the scientific community. In this research, we proposed to investigate the dynamics and performance of two multi-stage bench-scale anaerobic bioreactors (MSBSABs), operated under high salinity conditions (an intermediate salinity of 1.0% w/w as a control system, and a high salinity of 3.5% w/w as an experimental system). Both bioreactors were fed with the marine macroalgae, Sargassum spp., as energy biomass during an 18-week period of operations. The elemental composition of this energy biomass (dry sargassum) was lower than other fresh marine biomasses used in AD process. This was expected since the sargassum feedstock used in our study was harvested onshore and was already dried by the sun (beach wrack blend). The reduction of the volatile solids (VS) content within the control system was greater in the third chamber S3 (6.30± 1.79 g/100ml) than the VS content of the first chamber S1 (9.03± 2.83 g/100ml). A similar pattern was observed in the experimental system, which VS content was 6.90± 2.39 g/100ml in S3, compared to 10.25± 2.65 g/100ml in S1. A significant reduction of the mass fraction of macronutrients (C, H & N) was observed in both systems from the first chamber S1 to the last chamber S3. Nevertheless, the sulfur fraction of the third chamber S3 was higher in both bioreactors when comparing to that measured in S1. The biogas production was 30% greater in the control system (1.0% w/w) than the experimental system (3.5% w/w). The biogas yield averaged over time was a normalized rate of 91.05 ml of biogas per gram of VS fed per day in the experimental system, compared to a volumetric production of 132.42 ml of biogas per gram of VS fed per day in the control system. The biogas samples of both bioreactors presented a similar chemical composition to that reported for traditional freshwater anaerobic biodigesters. However, the biogas samples of the experimental bioreactor were of better quality in terms of methane concentration than the control bioreactor (with a methane percentage around 61.28± 1.70 for the experimental bioreactor, and 53.82± 5.10 for the control bioreactor).