The Holocene hydro-ecological and environmental change of the Nile Delta remains a knowledge gap. The study aimed to approach this objective by using multi-proxies of organic carbon (OC) in a well-dated MZ-1 core in Manzala lagoon off the Nile Delta. The data defined five distinctive stages at decadal-centennial scale. Stage I (ca. 8.2-7.7 ka) was characterized by remarkedly high reconstructed pH and low mean annual air temperature (the 8.2-ka cold event). The obviously low TOC and C/N, but higher short-chain n-alkanes indicated more marine OC deposition. This was followed by highly fluctuated organic geochemical proxies at Stage Ⅱ (ca. 7.7-5.8 ka) indicating episodic but significant terrestrial OC input delivered by Nile floods during the African Humid Period (AHP). Subsequent increase in short- and medium-chain n-alkanes suggested macrophytes prevailing in the lagoon during Stage Ⅲ (ca. 5.8-5.4 ka) with cooling-drying climate transitioned from the AHP. Stage Ⅳ (ca. 5.4-1.2 ka) witnessed decreased short-chain n-alkanes of marine origin and increased long-chain n-alkanes of terrestrial origin when the Nile climate entered into the mega-trend of aridification. Abnormal pulses of terrestrial OC with high TOC likely reflected the modified landscape due to early human occupation around the area. The highly fluctuated charcoal fluxes since ca. 6 ka implied such clearing-firing-aided land exploitation activity. The lagoon eco-setting was further affected by intensified anthropogenic-OC input after the latest millennium. Our study highlighted the land-ocean interactions on modulating the paleo-lagoonal ecology of the Nile Delta, which should be incorporated into healthy management in the Nile Delta.