Cesium (Cs) is widely applicated in the production of aeronautics, electronics, pharmacy, and catalysts. With the increasing demands for cesium resources by emerging technologies and the reduction of cesium ore, it is imperative to develop new cesium resources such as salt lake, geothermal, and oil & gas produced brine. Solvent extraction is a promising method for its advantages of continuous operation, simple equipment, and high throughout. The traditional extractants represented by calixarene crown ethers, and substituted phenols exhibit high Cs selectivity. 1,3-diisopropoxy calix[4]arene crown-6 (BPC6) is a typical calix[4]crowns which can coordinate with Cs+ ion with high affinity. Meanwhile, 4-tert-butyl-2-(α-methylbenzyl) phenol (t-BAMBP) is a kind of substituted phenol that selectively extracts Cs+ ions through ion exchange. However, both of them are limited for cesium isolation from brine due to the need for strong acid (1~4 mol/L HNO3) or basic (almost 1 mol/L NaOH) conditions. It is necessary to explore new extraction systems which apply in relatively mild conditions for liquid Cs resource applications. In this work, BPC6 and the t-BAMBP mixture were developed as a novel coordination-cation exchange coupling synergistic extraction system for the recovery of Cs(I) in weakly alkaline conditions of 30 mmol/L NaOH. The synergistic coefficient was calculated as 89.5 when the concentrations of BPC6 and t-BAMBP were 10 and 200 mmol/L, respectively. The synergistic extraction mechanism was discussed, and the thermodynamic parameters and equilibrium constants of the extraction reaction have been calculated. Moreover, stripping with only 10 mmol/L HCl produced a stripping efficiency of 84.1%. Besides, the effect of temperature on the stripping was investigated and 81.3% stripping efficiency can be achieved by heating at 313 K without any acidity solution. On this basis, a novel synergistic extraction and stripping system was established with the advantages that both the extraction and stripping can be carried out under mild conditions and obtained high potential in Cs(I) recovery of brine for its low acid-base consumption.