Coastal oceans link terrestrial and marine carbon cycles. Yet, carbon sources and sinks in these biomes remain poorly understood. Here, we explore the dynamics of dissolved organic matter (DOM) along the Amazon River-to-ocean continuum from the lower mainstem at Óbidos to the open ocean of the western tropical North Atlantic. We molecularly characterized DOM via ultrahigh-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), determined DOM stable carbon isotopes, and interpreted the data in the context of bacterial abundance and production, phytoplankton biomass and composition. Multivariate analysis revealed that the DOM molecular variability in the plume was mainly influenced by the input of terrigenous DOM. Incubation experiments with water from close to the river mouth showed that photo- and bio-degradation preferentially removed ¹³C-depleted and ¹³C-enriched terrigenous DOM, respectively. However, there was no significant quantitative change in the total amount of dissolved organic carbon (DOC) over five days. This result suggests that most of the reactive DOM had already been bio-degraded upstream within the river and that photo-degradation was diminished in the turbid plume close to the river mouth. Terrigenous DOM therefore appeared to be relatively non-reactive nearshore. In the less turbid offshore plume, enhanced light penetration stimulated growth of phytoplankton and increased bacterial production. Although marine DOM compounds became relatively enriched, bulk DOC concentrations were 9 to 30% below levels expected from conservative mixing of river and ocean endmembers suggesting that quantitative removal of terrigenous DOM was not compensated by marine DOM production. We propose that removal of terrigenous DOM in the outer plume may be enhanced by (i) bio-degradation primed by reactive algal DOM, (ii) photo-degradation, which may further break down DOM into more bio-available forms, and possibly (iii) sorption of DOM to sinking particles.