Purpose <p>To evaluate the associations between first-trimester inflammatory markers and gestational diabetes mellitus (GDM), including its subtypes and patterns, and to explore the role of these markers in the early identification of GDM risk.</p> Methods <p>This cohort study included pregnant women aged ≥ 18 years and &lt; 16 weeks of gestation, based on their first antenatal registration date, at a tertiary hospital from March to December 2023 retrospectively and from December 2023 to August 2024 prospectively. Inflammatory markers, calculated from peripheral blood cell counts, included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregated immune-inflammation index (AISI). Outcomes were GDM and its subtypes (isolated fasting hyperglycemia [IFH], isolated post-load hyperglycemia [IPH], and combined hyperglycemia [CH]), as well as patterns identified through latent class trajectory modeling based on blood glucose change during the OGTT.</p> Results <p>Among 4,426 eligible women, 821 developed GDM. Elevated first-trimester NLR, SII, SIRI, and AISI were significantly associated with higher GDM risk. Compared with non-GDM pregnant women, these markers were positively associated with both IPH (<i>OR</i>s range: 1.16–1.22) and CH (<i>OR</i>s range: 1.28–1.54), but not IFH, and with two OGTT glucose trajectories (medium-speed increase–rapid decrease group [<i>OR</i>s range: 1.20–1.25] and rapid increase–slow decrease group [<i>OR</i>s range: 1.31–1.68]), while no significant associations were observed for the other two trajectories.</p> Conclusion <p>First-trimester inflammatory markers are associated with more severe GDM phenotypes and may serve as potential biomarkers to inform the early identification of higher-risk GDM phenotypes.</p>