We investigated the relationships between inherent and apparent optical properties (IOP and AOP, respectively) and suspended sediment concentrations (SSC) in the main Amazonian river waters. In situ measurements of SSC, remote sensing reflectance (Rrs), the diffuse light attenuation coefficient (Kd) and the total and non-algal particle (NAP) absorption coefficients (aTOT and aNAP, respectively) were conducted during three sampling trips along different streams of the Amazon River catchment (104 stations). The size distribution and chemical characteristics of the suspended sediment were also determined for 85 stations. We show that the particle size distribution (PSD) in the river water is best described by a segmented Junge power law distribution with a smaller slope value for the smallest particles (J1 = 2.4) and a larger slope value (J2 = 4.1) for the largest particles (> 10 µm). A strong relationship was found between AOPs and IOPs and SSC when the entire data set was considered. However, for the Madeira River, the primary Amazon River tributary in terms of suspended sediment discharge, a significant dispersion was detected for the Rrs - SSC relationship but not for the Kd - SSC relationship. This dispersion has been shown by a previous study, using MODIS data, to display a seasonal pattern, which we investigated in this study using Mie modeling calibrated with suspended sediment characteristics. In the Madeira River, suspended sediment had a finer distribution size and a different mineralogy (e.g., a greater smectite content and a lower kaolinite content) during the rising water stage. Spectral variations of the imaginary part n'(λ) of the refraction index also showed significant differences during the rising water stage. In contrast, other streams of the Amazon basin had very stable properties with respect to granulometry and mineralogy. Model simulations made possible to reproduce both field and satellite observations, showing that the Rrs hysteresis observed in the Madeira River in the near infrared was mainly due to n'(λ) seasonal variations, leading to a decrease of absorption during the rising water stage. Kd was shown to remain stable because of its strong dependency on scattering processes. The model was used to further understand how suspended sediment size distribution and refraction index drive the IOPs in large rivers: n'(λ) variations were shown to control primarily the reflectance variability; Rrs(850) presented limited variations as a function of PSD in the range typical of large rivers (J1 < 3) although it remained sensitive to particle mineralogical composition; Rrs(670) showed the opposite behavior with a higher sensitivity to PSD variation for coarser PSD. Finally, we demonstrate that the use of the Rrs ratio between the red and infrared channels allowed a reduction of the Rrs sensitivity in all cases, by an average of 50% with respect to changes in the mineral composition or size distribution of suspended sediment. In particular, the Rrs ratio varied by less than 5% for PSD representative of surface river waters.