Cesium is an important strategic resource, and solvent extraction is the most frequently used technology for its extraction from various minerals and brines. However, this common method faces operational and cost problems owing to large alkali consumption. A synergistic extraction system consisting of 4-tert-butyl-2-(α-methylbenzyl) phenol (t-BAMBP) and di-(2-ethylhexyl) phosphoric acid (D2EHPA) was designed and used to extract Cs+ from an alkali-free solution. The effects of variables such as: (i) pH, (ii) concentration of t-BAMBP and D2EHPA, (iii) temperature, (iv) Cs+ concentration, and (v) coexisting cations, on the Cs+ extraction performance of the synergistic system were investigated. The most suitable organic phase composition was 1.0 mol/L t-BAMBP and 0.1 mol/L D2EHPA in kerosene, and the synergistic coefficient was up to 57 at 25 °C and an organic/aqueous phase volume ratio of 1/1. The extraction sequence of cations using the t-BAMBP–D2EHPA synergistic system followed the descending order Cs+ > Rb+ > Ca2+ > K+ > Li+ > Mg2+ > Na+. The chemical formula of the extracted species was determined as [CsA(HA)(ROH)2] using the slope method. The Cs+ extraction process is an exothermic reaction with an enthalpy (ΔHo) of −55.3 kJ mol−1, confirmed by the thermodynamic study. After three-stage countercurrent extraction, the extraction efficiency of Cs+ was 92.6%, demonstrating excellent selectivity from coexisting cations. The t-BAMBP–D2EHPA synergistic system showed outstanding economic and environmental advantages and a good application prospect to develop a conceptual process flowsheet for extraction with this system and stripping with HCl to separate cesium salt from salt-lake brine.