Background: The global incidence of ischemic stroke is projected to increase ~20% by 2030, with one-fifth of these cases attributed to cerebral small vessel disease (cSVD). Stiffening of central arteries potentiates small vessel injury in the brain, which may precede or develop in parallel with disruption of local regulatory mechanisms such as cerebrovascular reactivity. However, evidence of these vascular etiologies of cSVD remains inconclusive. To address this, we conducted separate systematic meta-analyses to characterize the relationship between cerebrovascular reactivity or arterial stiffness and cSVD. Methods: MEDLINE and Web of Science were searched for studies reporting odds ratios (OR) using arterial stiffness or cerebrovascular reactivity as continuous predictors for the presence of cSVD. Data were extracted using predefined tables and random-effects meta-analyses were performed to determine pooled OR and 95% confidence intervals. Results: Four cross-sectional studies were included in the analysis between cerebrovascular reactivity and cSVD, including 294 participants (38.1% women). Decrements in cerebrovascular reactivity were associated with a greater cSVD burden (OR = 1.93, 95% CI: 1.15-3.24, p = 0.01, I 2 = 97.4%). For arterial stiffness, 34 cross-sectional studies comprising of 26,541 participants (52.9% women) were included. Increases in indices of arterial stiffness were associated with a greater burden of cSVD (OR = 1.13, 95% CI: 1.07-1.20, p < 0.0001, I 2 = 60.2%). Conclusion: Impaired cerebrovascular reactivity and elevated arterial stiffness were both associated with an increased incidence of cSVD. While investigation of a link between cerebrovascular reactivity and arterial stiffness is a growing field, our findings suggest that the two measures have either individual or overlapping relationships with cSVD. This highlights the need for monitoring of both local and global cardiovascular regulation in high-risk individuals.