Aims: Type 2 diabetes (T2D) is a risk factor for ischemic stroke (IS) and associated with an adverse prognosis. Both stroke and diabetes care has evolved substantially during the last decade. This study aimed to determine the prevalence of T2D among IS patients along with time trends in the risk profile, use of glucose-lowering medications, quality-of-care and clinical outcomes, including stroke severity; length-of-stay; mortality, readmission and recurrent stroke in a large national cohort. Methods: Registry-based cohort study including all IS events in Denmark from 2004 to 2020. IS with co-morbid T2D were compared to IS without diabetes while adjusting for age, sex, stroke severity, co-morbidity and socio-economic factors. Results: The study included 169,262 IS events; 24,479 with co-morbid T2D. The prevalence of T2D in IS increased from 12.0% (2004–2006) to 17.0% (2019–2020). The adjusted absolute 30-day mortality risk in IS with T2D decreased from 9.9% (2004–2006) to 7.8% (2019–2020). The corresponding adjusted risk ratios (aRR) were 1.22 95% confidence interval (1.09–1.37) and 1.29 (1.11–1.50), respectively. The aRR of 365-day mortality was in 2004–2006: 1.20 (1.12–1.29) and in 2019–2020: 1.34 (1.22–1.47). The 30- and 365-day readmissions rates were also consistently higher in IS with T2D. Conclusions: The prevalence of T2D in IS increased over time. The 30- and 365-day mortality rates decreased over the time-period but were consistently higher in IS with co-morbid T2D. Readmissions were also higher in IS with T2D. This highlights an urgent need for strategies to further improve the prognosis in IS patients with co-morbid T2D.