The aim of this study was to analyze the influence of distinct production systems and seasonal variation in the Brazilian Eastern Amazon on the meat lipid composition of water buffaloes. Water buffaloes were reared in commercial farms in the Eastern Amazon either in extensive systems (Marajó Island, Nova Timboteua and Santarém locations), during rainy or dry seasons, or intensive (feedlot) systems. Animals reared in extensive systems were fed natural pastures, and those reared in feedlots were fed sorghum silage and commercial pellets. Buffaloes were slaughtered and ribeye muscle (longissimus lumborum) samples collected. Lipid-soluble antioxidant vitamins and fatty acids were analyzed. The nutritional value of meat from buffaloes reared in Marajó Island extensive system during the rainy season was higher than that of other systems, as it had lower levels of cholesterol and higher amounts of α-tocopherol associated with higher hypocholesterolaemic/hypercholesterolaemic ratio and lower index of atherogenic. Also, this meat had lower percentages of saturated fatty acids and higher proportions of mono- and polyunsaturated fatty acids (PUFA), particularly n − 3PUFA, with increased PUFA/saturated fatty acids ratio and decreased n − 6/ n − 3PUFA ratio. However, all extensive systems produced meat with a relatively low index of thrombogenicity values, which is advantageous for human health.