Background The American Heart Association's Life's Simple 7, a public health construct capturing key determinants of cardiovascular health, became the Life's Essential 8 after the addition of sleep duration. The authors tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle‐aged adults. Methods and Results The authors conducted a prospective magnetic resonance neuroimaging study in middle‐aged individuals without stroke or dementia enrolled in the UK Biobank. Self‐reported sleep duration was categorized as short (<7 hours), optimal (7–<9 hours), or long (≥9 hours). Evaluated neuroimaging markers included the presence of white matter hyperintensities (WMHs), volume of WMH, and fractional anisotropy, with the latter evaluated as the average of 48 white matter tracts. Multivariable logistic and linear regression models were used to test for an association between sleep duration and these neuroimaging markers. The authors evaluated 39 771 middle‐aged individuals. Of these, 28 912 (72.7%) had optimal, 8468 (21.3%) had short, and 2391 (6%) had long sleep duration. Compared with optimal sleep, short sleep was associated with higher risk of WMH presence (odds ratio, 1.11 [95% CI, 1.05–1.18]; P <0.001), larger WMH volume (beta=0.06 [95% CI, 0.04–0.08]; P <0.001), and worse fractional anisotropy profiles (beta=−0.04 [95% CI, −0.06 to −0.02]; P =0.001). Compared with optimal sleep, long sleep duration was associated with larger WMH volume (beta=0.04 [95% CI, 0.01–0.08]; P =0.02) and worse fractional anisotropy profiles (beta=−0.06 [95% CI, −0.1 to −0.02]; P =0.002), but not with WMH presence ( P =0.6). Conclusions Among middle‐aged adults without stroke or dementia, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because these neuroimaging markers precede stroke and dementia by several years, these findings are consistent with other findings evaluating early interventions to improve this modifiable risk factor.