A single gene can give rise to multiple functionally distinct forms of protein molecules, called proteoforms, originating from gene mutations, RNA alternative splicing, polymorphisms, and post-translational modifications (PTMs). It is essential to characterize proteins in a proteoform-specific manner to improve our understanding of their role in health and disease. Mass spectrometry (MS)-based top-down proteomics (TDP) has emerged as a powerful tool for the characterization of proteoforms by coupling high-efficiency liquid-phase separation techniques to high-resolution MS and tandem MS (MS/MS). Capillary zone electrophoresis (CZE)-MS is one such separation technique offering unique advantages compared to conventional liquid chromatography (LC)-MS methods, including highly efficient separations of proteoforms based on electrophoretic mobility (µep), minimal sample and solvent consumption, high sensitivity for proteoform detection, and ease of predicting proteoforms’ µep. In this work, research teams from around the world joined forces to validate the robustness and reproducibility of CZE-MS for TDP in both simple and complex model proteoform mixtures, comparing its performance with state-of-the-art LC-MS methods. This study encompasses a full spectrum of commercially available CE-MS interfaces and CE and MS instrumentation amenable to TDP analysis. We provide a repository of CZE-MS methods and detailed experimental protocols for robust, reproducible, and sensitive CE-MS-based TDP analysis that were evaluated by several laboratories. We expect this study will offer the proteomics community an informative resource of ready-to-use experimental CE-MS techniques and a better understanding of the CZE-MS approach and its potential in TDP, which together will accelerate the broad adoption of CZE-MS in protein and proteoform research.