Current conversations in literacy research call for the need to consider children’s social-emotional development and academic learning in an integrated way that honors and supports the whole child in their cultural context. Here we review available literatures on the cognitive, linguistic, affective, social and cultural dimensions of typical and atypical reading acquisition and what is known of their neural correlates. From this review, and in consultation with neuro- and psychological scientists and expert educators working in a range of contexts, we derive a series of interdisciplinary Learnings. These describe what is known about how diverse children grow into readers and how literacy development can be optimally supported in school, home and community contexts across the first decades of life. The Learnings together provide a critical cross-disciplinary synthesis of how literacy and social-emotional development are coordinated, individually variable, dynamic and sensitive to contextual influences. They reveal how evidence-based, culturally inclusive, socially attentive and developmentally appropriate instruction is an essential piece of helping every child organize their brain and mind for literacy. Such comprehensive instruction is necessary to address inequities in general and special education, and to help children become fully literate—a designation that goes beyond simply decoding and comprehending text. Impacts of digital technology, and other timely issues and open questions, are also discussed.