Mesoderm arises at gastrulation and contributes to both the mouse embryo proper and its extra‐embryonic membranes. Two‐photon live imaging of embryos bearing a keratin reporter allowed recording filament nucleation and elongation in the extra‐embryonic region. Upon separation of amniotic and exocoelomic cavities, keratin 8 formed apical cables co‐aligned across multiple cells in the amnion, allantois, and blood islands. An influence of substrate rigidity and composition on cell behavior and keratin content was observed in mesoderm explants. Embryos lacking all keratin filaments displayed a deflated extra‐embryonic cavity, a narrow thick amnion, and a short allantois. Single‐cell RNA sequencing of sorted mesoderm cells and micro‐dissected amnion, chorion, and allantois, provided an atlas of transcriptomes with germ layer and regional information. It defined the cytoskeleton and adhesion expression profile of mesoderm‐derived keratin 8‐enriched cells lining the exocoelomic cavity. Those findings indicate a novel role for keratin filaments in the expansion of extra‐embryonic structures and suggest mechanisms of mesoderm adaptation to the environment. Synopsis: Keratin intermediate filaments form apical cables continuous across multiple cells in mesoderm‐derived extra‐embryonic tissues lining the exocoelomic cavity of the mouse embryo. Loss of keratin results in defective growth of extra‐embryonic membranes. At late gastrulation, keratin filaments nucleate, elongate, and co‐align across multiple cells.In explanted mesoderm cells, cell speed and keratin content vary according to the composition and rigidity of the substrate.Embryos devoid of keratin filaments have a smaller cavity, amnion, and allantois.A single cell transcriptomic atlas of extra‐embryonic membranes defines early differentiation of clusters in extra‐embryonic mesoderm, amnion, chorion, and allantois. [ABSTRACT FROM AUTHOR]