The seas of Southeast Asia are home to some of the world’s most diverse ecosystems and resources that support the livelihoods and wellbeing of millions of people. Climate change will bring temperature changes, acidification and other environmental change, with uncertain consequences for human and natural systems in the region. We present the first regional-scale projections of change in the marine environment up to the end of 21st century. A coupled physical-biogeochemical model with a resolution of 0.1° (approximately 11 km) was used to create projections of future environmental conditions under two greenhouse gas scenarios, RCP4.5 and RCP8.5. These show a sea that is warming by 1.1–2.9°C through the 21st century, with surface pH falling by up to 0.02 and dissolved oxygen decreasing by 5 to 13 mmol m− 3. Changes for different parts of the region, including four sensitive coastal sites, are presented. The changes reach all parts of the water column and many places are projected to experience conditions well outside the range seen at the start of the century. Altered species distribution and damage to coral reefs resulting from this environmental change would have consequences for biodiversity, for the livelihoods of small-scale fishers and for the food security of coastal communities across the region. Projections of this type are a key tool for communities planning how they will adapt to the challenge of climate change.