In this article, we examine the general space‐time fractional diffusion equation for left‐invariant hypoelliptic homogeneous operators on graded Lie groups. Our study covers important examples such as the time fractional diffusion equation, the space‐time fractional diffusion equation when diffusion is under the influence of sub‐Laplacian on the Heisenberg group, or general stratified Lie groups. We establish the global well‐posedness of the Cauchy problem for the general space‐time fractional diffusion equation of the Rockland operator on a graded Lie group in the associated Sobolev spaces and also develop some regularity estimates for it.