Escherichia coliis a leading cause of invasive bacterial infections in humans. Capsule polysaccharide has an important role in bacterial pathogenesis, and the K1 capsule has been firmly established as one of the most potent capsule types inE. colithrough its association with severe infections. However, little is known about its distribution, evolution and functions across theE. coliphylogeny, which is fundamental to elucidating its role in the expansion of successful lineages. Using systematic surveys of invasiveE. coliisolates, we show that the K1-cpslocus is present in a quarter of bloodstream infection isolates and has emerged in at least four different extraintestinal pathogenicE. coli(ExPEC) phylogroups independently in the last 500 years. Phenotypic assessment demonstrates that K1 capsule synthesis enhancesE. colisurvival in human serum independent of genetic background, and that therapeutic targeting of the K1 capsule re-sensitizesE. colifrom distinct genetic backgrounds to human serum. Our study highlights that assessing the evolutionary and functional properties of bacterial virulence factors at population levels is important to better monitor and predict the emergence of virulent clones, and to also inform therapies and preventive medicine to effectively control bacterial infections whilst significantly lowering antibiotic usage.