Introduction: Stroke is associated with major consequences in terms of socioeconomic impact and lost disability-adjusted life in young victims, thus justifying a careful surveillance of epidemiological trends. This study aimed to assess changes in the incidence of ischemic stroke in young adults over a long period. Methods: All cases of first-ever ischemic stroke that occurred among adults aged 18–55 years were prospectively recorded using the population-based Dijon Stroke Registry, from 1985 to 2017. Sex-specific annual incidence rates were calculated and were presented according to 6 time periods. Incidence rate ratios (IRRs) were determined to assess sex differences in stroke incidence. Results: Over the whole study period, 4,451 patients suffered a first-ever ischemic stroke. Among these patients, 469 (10.5%) were young adults (median age: 46 years, IQR: 39–50; 53.9% men). Incidence rates rose from the study period 2003 to 2007 compared with previous periods and remained stable thereafter, both in men and women. Hence, incidence per 100,000 per year was globally 11.0 (95% CI: 9.4–12.7) before 2003 and 22.9 (20.3–25.6) thereafter. In individuals aged 18–45 years, incidence rates were 5.4 (4.3–6.9) overall, 4.1 (2.7–6.0) in men, and 6.7 (4.9–9.0) in women, before 2003. After 2003, incidence rates rose to 12.8 (10.7–15.1) overall, 12.0 (9.2–15.4) in men, and 13.6 (10.6–17.0) in women. In this age group, the men/women IRR was 0.78 (95% CI: 0.62–1.26, p = 0.08), although sex differences decreased over time (IRR = 0.62; 95% CI: 0.36–1.02, p = 0.046 before 2003, vs. IRR = 0.88; 95% CI: 0.62–1.26, p = 0.48 after 2003). In individuals aged 45–55 years, incidence rates before 2003 were 47 (37–61) in men and 25 (17–35) in women (IRR = 1.90; 95% CI: 1.24–2.97, p < 0.001), and they increased to 82 (67–100) in men and 46 (35–59) in women (IRR = 1.79; 95% CI: 1.29–2.49, p < 0.001) after 2003. Conclusions: The incidence of ischemic stroke in young adults increased during the early 2000s and remained stable thereafter. These results highlight the priority need for dedicated prevention strategies for the young to reduce the burden of stroke.