The Mackey-Zimmer theorem classifies ergodic group extensions X of a measure-preserving system Y by a compact group K, by showing that such extensions are isomorphic to a group skew-product X ≡ Y ⋊ρ H for some closed subgroup H of K. An analogous theorem is also available for ergodic homogeneous extensions X of Y , namely that they are isomorphic to a homogeneous skew-product Y ⋊ρ H/M . These theorems have many uses in ergodic theory, for instance playing a key role in the Host-Kra structural theory of characteristic factors of measure-preserving systems.The existing proofs of the Mackey-Zimmer theorem require various "countability", "separability", or "metrizability" hypotheses on the group Γ that acts on the system, the base space Y , and the group K used to perform the extension. In this paper we generalize the Mackey-Zimmer theorem to "uncountable" settings in which these hypotheses are omitted, at the cost of making the notion of a measure-preserving system and a group extension more abstract. However, this abstraction is partially counteracted by the use of a "canonical model" for abstract measure-preserving systems developed in a companion paper. In subsequent work we will apply this theorem to also obtain uncountable versions of the Host-Kra structural theory.