The opportunistic bacterium Escherichia coli can invade normally sterile sites in the human body, which leads to life-threatening organ dysfunction and even death. However, our understanding of the evolutionary processes that shape its genetic diversity in this sterile environment remains limited. Here, we aim to quantify the frequency and characteristics of homologous recombination in E. coli from bloodstream infections. Analysis of 557 short read genome sequences revealed that the propensity to exchange DNA by recombination varies within a distinct population (bloodstream) at narrow geographical (Dartmouth-Hitchcock Medical Center, New Hampshire, USA) and temporal (years 2016 – 2022) scope. We identified four largest monophyletic sequence clusters in the core genome phylogeny that are represented by prominent STs: BAPS1 (mainly ST95), BAPS4 (mainly ST73), BAPS10 (mainly ST131), BAPS14 (mainly ST58). We show that the four dominant clusters vary in the characteristics of recombination: single nucleotide polymorphisms due to recombination, number of recombination blocks, cumulative bases in recombination blocks, ratio of probabilities that a given site was altered through recombination and mutation (r/m), and ratio of rates at which recombination and mutation occurred (r/q). Each sequence cluster contains a unique set of recombined AMR and virulence genes. Common among the four sequence clusters were the recombined virulence genes with functions associated with the Curli secretion channel (csgG) and ferric enterobactin transport (entEF, fepEG). We did not identify any one recombined antimicrobial resistance (AMR) gene that was present in all four sequence clusters. However, AMR genes mdtABC, baeSR, emrKY and tolC had experienced recombination in sequence clusters BAPS4, BAPS10, and BAPS14. These results demonstrate that the impact of homologous recombination is highly variable even among clonally related individuals, contributing to the remarkable genetic diversity and pathogenic potential that exists in the entire local population. Such genetic variation can impact the capability of specific E. coli lineages to cause bloodstream infections and their response to clinical interventions.