One-step fractional extraction was developed to selectively extract (-)-epicatechin-3-gallate (ECG) from tea polyphenols (TP) by using centrifugal contactor separators (CCSs). An efficient extraction system was constructed without reactive extractant. A model for fractional extraction was set up to study the effect of feed position, the number of stages (NTU), and phase ratio on extraction performance. Residual rate (R) was introduced to optimize the separation of low-concentration substance from complex tea polyphenols. Simulation and optimization are utilized to obtain the optimal parameters for separation of ECG from tea polyphenols. ECG has been separated by one-step fractional extraction with high purity of 98%, yield of 94%, and output of 397 g in 24 h, which is very promising for carrying out industrial production owing to continuous separation and low operation cost. The method has potential to separate objective substance with low content from multicomponent mixtures in an industrial scale.