Molecular size is a critical parameter for characterizing dissolved organic matter in aquatic systems. Four cruises were conducted in October 2018, March 2019, July 2019 (with a normal flood), and August 2020 (with an extreme flood), along a transect from the Changjiang (Yangtze) River freshwater to the shelf area with salinities near or > 30. During each cruise surface water samples at 5–6 stations were collected along the salinity gradient, and absorption spectra (to quantify and qualify chromophoric dissolved organic matter (CDOM)) were measured. In addition, ultrafiltration was conducted so that the size partitions including four factions of <1 kDa, 1–3 kDa, 3–10 kDa and 10 kDa–0.2 μm were obtained. In the different seasons, CDOM molecular sizes always showed decreasing trends from land to sea, which was consistent to most estuaries worldwide. In the freshwaters, those with sizes >1 kDa generally contributed 20%–40% of the bulk CDOM in different seasons, but these large colloidal molecules always disappeared at the offshore stations. The extreme flood in August 2020 brought more waters with lower salinity and higher CDOM concentration into the transects, and the extra CDOM materials were generally of larger molecular sizes. In addition to suspended particulate matter (SPM) resuspension, the flocculation of organic matter could also be another important reason for localised increased CDOM molecular size near the river mouth.