The integration of sedimentary facies, pollen, spores, carbon and nitrogen isotopes records, C/N ratio and radiocarbon dates allowed the identification of changes in vegetation and the sources of organic matter accumulated on tidal flats near the mouth of the Amazon River during the mid and late Holocene. Data from the margin of Amazon River indicate marine influence related to mangrove presence over a tidal mud flat between 5560–5470 cal. yr BP and 5290–5150 cal. yr BP. Afterward, the mangrove area shrank following the return of more humid conditions and increase of Amazon River discharge. A common reworking process of the tidal flat through the lateral migration of a meandering creek occurred in the study site, with later development of transitional vegetation under freshwater influence. Following the natural vegetation succession under stable climate and hydrological conditions, the expansion of ‘várzea’ (flooded freshwater vegetation) forests occurred since 600–560 cal. yr BP until the present. Furthermore, regarding the tidal flats located west of the mouth of Amazon River, these stable conditions also allowed the mangrove maintenance over mudflats with deposition of marine organic matter during at least the last 2350–2300 cal. yr BP.