The key difference between 2D and 3D graphics lies in dimensionality. 2D graphics are flat images represented in two dimensions, using height and width, ideal for illustrations, logos, and games. In contrast, 3D graphics incorporate depth along with height and width, allowing for more realistic representations of objects in space. This enables features like rotation, scaling, and lighting effects, making 3D graphics essential for applications such as animation, gaming, and virtual reality.