Extraintestinal pathogenic Escherichia coli (ExPEC) causes invasive E. coli disease (IED), including bacteraemia and (uro)sepsis, resulting in a high disease burden, especially among older adults. This study describes the epidemiology of IED in England (2013–2017) by combining laboratory surveillance and clinical data. A total of 191 612 IED cases were identified. IED incidence increased annually by 4.4–8.2% across all ages and 2.8–7.6% among adults ≥60 years of age. When laboratory-confirmed urosepsis cases without a positive blood culture were included, IED incidence in 2017 reached 149.4/100 000 person-years among all adults and 368.4/100 000 person-years among adults ≥60 years of age. Laboratory-confirmed IED cases were identified through E. coli-positive blood samples (55.3%), other sterile site samples (26.3%), and urine samples (16.6%), with similar proportions observed among adults ≥60 years of age. IED-associated case fatality rates ranged between 11.8–13.2% among all adults and 13.1–14.7% among adults ≥60 years of age. This study reflects the findings of other published studies and demonstrates IED constitutes a major and growing global health concern disproportionately affecting the older adult population. The high case fatality rates observed despite available antibiotic treatments emphasize the growing urgency for effective intervention strategies. The burden of urosepsis due to E. coli is likely underestimated and requires additional investigation.