Human beings may have evolved the largest asymmetries of brain organization in the animal kingdom. Hemispheric left-vs-right specialization is especially pronounced in species-unique capacities, including emotional processing such as facial judgments, language-based feats such as reading books, and creativity such as musical performances. We hence chart the largest longitudinal brain-imaging resource, and provide evidence that brain asymmetry changes continuously in a manner suggestive of neural plasticity throughout adulthood. In the UK Biobank population cohort, we demonstrate that whole-brain patterns of asymmetry changes show robust phenome-wide associations across 959 distinct variables spanning 11 categories. We also find that changes in brain asymmetry over years co-occur with changes among specific lifestyle markers. We uncover specific brain asymmetry changes which systematically co-occur with entering a new phase of life, namely retirement. Finally, we reveal relevance of evolving brain asymmetry within subjects to major disease categories across ~4500 total medical diagnoses. Our findings speak against the idea that asymmetrical neural systems are conserved throughout adulthood.