The weaning transition from milk to solid foods represents a critical developmental window characterised by profound changes in the infant gut microbiome and lipid metabolism (1). During this period, the maturing microbiota metabolises complex lipids, influencing host lipid homeostasis (2). This study aims to characterise changes in the infant faecal lipidome and gut microbiome in response to early-life feeding practices, including exclusive versus non- exclusive breastfeeding (EBF) and the transition to solid foods. Faecal samples were collected from infants (n = 28) across three dietary transition stages: pre-weaning (PREW), 4 weeks (WK04) and 12 months (LATW) post solid-introduction. Untargeted lipidomics using LC-MS/MS was performed to characterise faecal lipid profiles, with differential lipids identified based on variable importance in projection (VIP) and fold change (FC). Full-length 16S rRNA gene amplicon sequencing was used to characterise microbiome composition, followed by correlation analysis to assess associations between microbial taxa and differential lipids. At pre-weaning, non-EBF infants exhibited significantly higher levels of faecal phosphatidylethanolamine (PE), N-acyl lyso-phosphatidylethanolamines (LNAPE), and N-acyl ethanolamines (NAE) as compared to EBF infants (VIP > 1.0, |log₂FC| > 1, p < 0.05) consistent with altered NAE biosynthesis and bioactive lipid signalling. PE and LNAPE were negatively correlated with Faecalimonas, Phocaeicola, and Bacteroides (p < 0.05), linking differences in phospholipid metabolism with gut microbial composition. Following solid food introduction, principal component analysis (PCA) of lipidomic profiles showed distinct separation between pre- and post-weaning EBF infants (PERMANOVA: F = 14.07, R² = 0.48, p < 0.05). At four weeks post-introduction, PE, LNAPE and NAE were significantly enriched (VIP > 1.0, |log₂FC| > 1, p < 0.05), indicating a transient shift in NAE-associated bioactive lipid metabolism during the transition to solid foods. By late weaning, NAE levels were no longer significantly enriched relative to pre-weaning levels. In post-weaning EBF infants, Faecalibacterium was positively correlated with both PE and LNAPE (p < 0.05), suggesting an association between the emerging gut microbiota and phospholipid metabolism during weaning. In contrast, non-EBF infants exhibited a more gradual lipidomic transition, with significant separation from pre-weaning profiles emerging only at late weaning (PERMANOVA: F = 4.52, R² = 0.23, p < 0.05). This transition was accompanied by persistent enrichment of ceramide alpha-hydroxy fatty acid–phytosphingosines (Cer_AP; p < 0.05), indicating sustained alterations in sphingolipid metabolism. In conclusion, pre-weaning feeding practices drive distinct microbiome-lipid trajectories during the transition to solid foods. Exclusive breastfeeding was characterised by a dynamic response involving transient alterations in NAE-related metabolism and positive associations between Faecalibacterium and PE and LNAPE, whereas non-exclusive breastfeeding showed earlier NAE-related alterations and persistent sphingolipid enrichment. These findings highlight early nutrition's critical role in shaping gut microbial and lipid metabolic development during infancy.