CO2 sequestration in deep saline aquifers is being intensively studied as a strategy to mitigate CO2 emission. When CO2 is injected into the saline aquifers, a series of physical and chemical reactions will take place with the brine and rock skeleton under the multiple effects of salinity, temperature, pressure, hydrodynamic and chemistry to achieve the long-term underground storage of CO2. Therefore, we used an etched homogenous glass micromodel to investigate the impact of salinity on the brine-saturated reservoirs at the CO2 injection rate of 0.05 ml·min−1, temperature 25 °C, and pressure 0.1 MPa. Five brine concentrates were set in our experiment: 0 mol/l, 1 mol/l, 2 mol/l, 3 mol/l, and 4 mol/l to represent different types of saline aquifers. Based on the experimental results, a detailed discussion about the mode transformation of displacement, CO2 saturation and wettability variation, differential pressure change between inlet and outlet was made. The major contribution of salinity is to change the viscosity of brine, which will then affect other physicochemical properties to furtherly change the behavior of microfluidics. The effect of salinity on the drainage process was analyzed specifically in this study. It was found that as the salinity improved, the capillary number increased to make the displacement mode change from capillary fingering to viscous fingering. When the viscous force was dominant, the saturation of residual brine became bigger and the variation of wettability was not obvious. At the same time, the maximum pressure promoting the displacement finished needed to be bigger as the salinity improved to overcome more viscous force. Finally, it was found that in the brine with higher salinity, salt precipitation was more obvious.