Background: The relationships between food environments and dietary intake have been assessed via a range of methodologically diverse measures of spatial exposure to food outlets, resulting in a largely inconclusive body of evidence, limiting informed policy intervention. Objective: This systematic review aims to evaluate the influence of methodological choice on study outcomes by examining the within-study effect of availability (e.g., counts) versus accessibility (e.g., proximity) spatial exposure measures on associations with diet. Methods: (PROSPERO registration: CRD42018085250). PubMed, Web of Science, Scopus and ScienceDirect databases were searched for empirical studies from 1980 to 2017, in the English language, involving adults and reporting on the statistical association between a dietary outcome and spatial exposure measures of both availability and accessibility. Studies were appraised using an eight-point quality criteria with a narrative synthesis of results. Results: A total of 205 associations and 44 relationships (i.e., multiple measures of spatial exposure relating to a particular food outlet type and dietary outcome) were extracted from 14 eligible articles. Comparative measures were dominated by counts (availability) and proximity (accessibility). Few studies compared more complex measures and all counts were derived from place-based measures of exposure. Sixteen of the 44 relationships had a significant effect involving an availability measure whilst only 8 had a significant effect from an accessibility measure. The largest effect sizes in relationships were mostly for availability measures. After stratification by scale, availability measure had the greatest effect size in 139 of the 176 pairwise comparisons. Of the 33% (68/205) of associations that reached significance, 53/68 (78%) were from availability measures. There was no relationship between study quality and reported study outcomes. Conclusions: The limited evidence suggests that availability measures may produce significant and greater effect sizes than accessibility measures. However, both availability and accessibility measures may be important concepts of spatial exposure depending on the food outlet type and dietary outcome examined. More studies reporting on multi-method effects are required to differentiate findings by the type of spatial exposure assessment and build an evidence base regarding the appropriateness and robustness of measures under different circumstances.