The formation mechanism of secondary microplastics (issued from larger plastics) in the oceans is still an open question. However, it is commonly accepted that the chemical degradation undergone by polymers leads to their embrittlement and finally fragmentation. In the marine environment, polymers are subjected to different types of chemical and physical degradations. This study focuses on the coupling between two types of chemical degradation: hydrolysis and oxidation in the case of polyamide 6. To do so, polymer films (250 µm thick) were aged for durations up to 2 years and then characterized at the molecular scale using FTIR and at the macromolecular scale using mainly DSC and GPC. Results clearly show the existence of a chemical coupling between oxidation and hydrolysis in polyamide 6 that induces a large increase in the chain scission rate. The degradation rate is indeed 80 times faster in water with oxygen than in water without oxygen. Then, a two-stage ageing condition (first thermal oxidation in dry air and then hydrolysis in water without oxygen) was used to further study the nature of the coupling. These results have shown for the first time that a strong interaction occurs between thermal oxidation and hydrolysis of polyamide materials at the macromolecular scale.