Hydrochemistry and strontium isotope data were analysed in water samples from the Xi River Drainage system to reveal the spatial and seasonal variations in chemical weathering, associated CO2 consumption fluxes, and their control factors. The main ions were Ca2+, Mg2+, and HCO3−, which are characteristic of a drainage system on carbonate-dominated bedrock. The dissolved loads were derived from four major end-member reservoirs: silicate, limestone, dolomite, and atmosphere. The silicate weathering rates (SWRs) increased downstream from 0.03 t/km2/year to 2.37 t/km2/year. The carbonate weathering rates (CWRs) increased from 2.14 t/km2/year in the upper reaches, to 32.65 t/km2/year in the middle reaches, and then decreased to 23.20 t/km2/year in the lower reaches. The SWR values were 281.38 and 113.65 kg/km2/month during the high- and low-water periods, respectively. The CWR values were 2456.72 and 1409.32 kg/km2/month, respectively. The limestone weathering rates were 2042.74 and 1222.38 kg/km2/month, respectively. The dolomite weathering rates were 413.98 and 186.94 kg/km2/month, respectively. Spatial and seasonal variations in chemical weathering were controlled mainly by lithology, vegetation, and climate (temperature, water discharge, and precipitation). The CO2 consumption flux by chemical weathering was estimated at 189.79 × 109 mol/year, with 156.37 × 109 and 33.42 × 109 mol/year for carbonate and silicate weathering, respectively. The CO2 fluxes by chemical weathering are substantially influenced by sulfuric acid in the system. The CO2 flux produced by sulfuric acid weathering was estimated at 30.00 × 109 mol/year in the basin. Therefore, the Xi River Basin is a CO2 sink with a net consumption of CO2 flux of 3.42 × 109 mol/year.