Based on the canonical quantization of d ≥ 2 dimensional General Relativity (GR) via the Dirac constraint formalism (also termed as 'constraint quantization'), we propose the loss of covariance as a fundamental property of the theory. This breakdown occurs for the first-order Einstein Hilbert action, whereby besides first class constraints, second class constriants also exist leading to non-standard ghost fields which render the path integral non-covariant. For the Hamiltonian formulation of GR, only first class constraints exist, however, the loss of covariance still happens due to structures arising from non-covariant constraints in the path integral. In contrast, covariance is preserved when constraint quantization is conducted for non-Abelian gauge theories, such as the Yang-Mills theory. Hence, we infer that the breakdown in space-time is a property of GR itself (for d ≥ 2 dimensions). Covariance is recovered and quantization and perturbative calculations are possible in the weak limit of the gravitational field of these actions. Hence, we further propose that the breakdown of space-time occurs as a non-perturbative feature of GR in the strong limit of the theory. These findings are novel from a canonical gravity formalism standpoint, and are consistent with GR singularity theorems which indicate breakdown at a strong limit of the field. They also support emergent theories of spacetime and gravity, though do not require thermodynamics such as entropic gravity. From an effective field theory view, these indicate that new degrees of freedom in the nonperturbative sector of the full theory are a requirement, whereby covariance as a symmetry is broken in the high energy (strong field) sector. Our findings are also consistent with the recent resolution of the information loss paradox in black holes.