In the late 20th century, global warming consumes 75% of the world habitable land, forcing mankind to build new, raised cities above those that are now claimed by the sea. But the flooding has not only claimed land. Millions of people have been killed as well, leaving humanities workforce severely depleted and as a result, have created a robotic workforce to handle the workload. To govern how this robotic workforce is treated, the UN creates the "New Geneva Convention", part of which is clause 21, which forbids robots that can pass as humans from being created, which are dubbed "hollow children" by the population. To enforce clause 21, the UN creates specialist R.U.S.T crews. When a hollow child breaks into the headquarters of robotics company Bergen, after discovering he is a hollow child and having lived his life believing himself to be human, the UN suspect the Amada corporation to be behind its creation. As a result, a R.U.S.T crew is dispatched to bring Amada's CEO before the UN security council to give answers.

Binary Domain puts the player in the role of Dan Marshall, leader of the R.U.S.T team sent to Tokyo to apprehend Amada CEO. Gameplay revolves around third person, squad based, cover based combat. Players will be largely engaging with armies of robots dispatched by Amada to stop them, but instead of just simply being able to shot and kill the robots, they can strategically dismember them, removing their arms will prevent them from shooting, taking out their legs will slow them, etc. However, this may not put them down permanently, at which point extra work will have to be put in.

As this is also a squad based game, players will also be able to use your squad to help you take down some of the larger opponents by getting them to concentrate fire onto specific points. Binary Domain also has voice recognition, so players can also issue voice commands to AI squad mates if they have a headset to do it with. Without a headset, the standard controller for each console will have commands attached to certain buttons. AI squad mates will also have a 'Trust Meter', which shows how much they trust the player with there life, the higher the trust meter, the more risk they will be willing to take. The meter can be filled or emptied during combat, as well as by giving right or wrong answers during conversations that take place during levels.