Using a combined approach of seafloor mapping, MAPR and CTD survey, we report evidence for active hydrothermal venting along the 130°-140°E section of the poorly-known South-East Indian Ridge (SEIR) from the Australia-Antarctic Discordance (AAD) to the George V Fracture Zone (FZ). Along the latter, we report Eh and CH4 anomalies in the water column above a serpentinite massif, which unambiguously testify for ultramafic-related fluid flow. This is the first time that such circulation is observed on an intermediate-spreading ridge. The ridge axis itself is characterized by numerous off-axis volcanoes, suggesting a high magma supply. The water column survey indicates the presence of at least ten distinct hydrothermal plumes along the axis. The CH4:Mn ratios of the plumes vary from 0.37 to 0.65 denoting different underlying processes, from typical basalt-hosted to ultramafic-hosted high-temperature hydrothermal circulation. Our data suggest that the change of mantle temperature along the SEIR not only regulates the magma supply, but also the hydrothermal activity. The distribution of hydrothermal plumes from a ridge segment to another implies secondary controls such as the presence of fractures and faults along the axis or in the axial discontinuities. We conclude from these results that hydrothermal activity along the SEIR is controlled by magmatic processes at the regional scale and by the tectonics at the segment scale, which influences the type of hydrothermal circulation and leads to various chemical compositions. Such variety may impact global biogeochemical cycles, especially in the Southern Ocean where hydrothermal venting might be the only source of nutrients.