Background The cortical plate (future cortex) is readily identifiable in utero at MRI. However, MRI evaluation of the remaining brain layers is limited by the poor T2 contrast between the subplate and the underlying intermediate zone (IZ). Purpose To compare the delineation of fetal brain lamination between T2-weighted single-shot fast spin-echo (SSFSE) and echo-planar imaging (EPI) fluid-attenuated inversion recovery (FLAIR) images, and to quantify differences in the depiction of brain layering between the two sequences. Materials and Methods Consecutive fetal brain MRI examinations performed between January 2014 and March 2018 with T2-weighted SSFSE and EPI-FLAIR images were reviewed. Two neuroradiologists evaluated the visibility of brain layers by using a three-point grading system, and findings were compared by using the sign test. One rater performed region-of-interest analysis in the cortical plate (CP), subplate (gyral crest and sulcal bottom), and IZ. Signal intensity (SI) ratios between adjacent brain compartments were calculated and compared by using the paired t test. Reader agreement was assessed by using weighted κ values. Results A total of 259 MRI examinations (mean gestational age [GA], 26.9 weeks ± 5.6) were included in the qualitative analysis, and 72 MRI examinations (mean GA, 27.4 weeks ± 5.5) were included in the quantitative analysis. Subplate identification on EPI-FLAIR images was superior to that on T2-weighted SSFSE images (subplate visualization [complete + partial]: frontal lobe, n = 243 vs n = 117; temporal lobe, n = 244 vs n = 137; parietal lobe n = 240 vs n = 93; and occipital lobe, n = 241 vs n = 97, respectively; P < .001), with higher interrater reliability (κ = 0.91-0.95 for EPI-FLAIR images and 0.80-0.87 for T2-weighted SSFSE images). SI ratios between the IZ and subplate were significantly higher on EPI-FLAIR images in all lobes (EPI-FLAIR images: 1.6-2.1; T2-weighted SSFSE images:1.2-1.2; P < .001). Subplate-to-CP ratios were not statistically significant between the two sequences (EPI-FLAIR:1.8-2.4; T2-weighted SSFSE: 2.0-2.2; P < .001). Conclusion The echo-planar fluid-attenuated inversion recovery sequence improves visualization of fetal brain lamination compared with the T2-weighted single-shot fast spin-echo sequence, as established by quantitative and qualitative methods. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Rossi in this issue.