Based on the daily cloud cover derived from the 1078-gauge stations in eastern China during 1961-2003, the temporal-spatial characteristics of the leading mode of winter cloudy day frequency (CDF) over eastern China are revealed via Empirical Orthogonal Function analysis. We revealed the two influence routes of this leading mode, based on which the physical-motivated empirical model is conducted to the seasonal prediction of the winter CDF in eastern China. The results show that: (1) the first EOF mode of winter CDF explains the 59% of the total variance, which is significant and independent from the other modes. This mode mainly shows a homogenous spatial pattern over eastern China and presents a dominant interannual variability. In the positive phase of this mode, a significant lower-level anticyclonic circulation anomaly appears over North Pacific. The anomalous southerly wind over the western flank of the anticyclonic could transport water vapor from tropical ocean to eastern China, leading to increased CDF; (2) the preceding persistent North Pacific subtropical SSTA dipole pattern (NPD) during August and September, and lowing of sea level pressure over midlatitude North Atlantic (LPA) from September to November are the two independent drivers for the formation and variation of this mode. The cold SSTA in the western pole of the NPD is advected southward to the tropical western Pacific by the anomalous northerly of the local low-level anomalous cyclone, and the Bjerknes feedback is then formed which further maintains and accelerates “west cold east warm” zonal SSTA dipole pattern in tropical Pacific. This tropical Pacific zonal SSTA pattern stimulates zonal convection dipole, which further induces a meridional atmospheric teleconnection in the North Pacific. The southerly over the west of the anomalous North Pacific anticyclone is conducive to more CDF in eastern China. The LPA reflects the transition of quasi-stationary Rossby wave train in mid-high latitudes Eurasia from autumn to winter. In winter, the southerly on the west of the barotropic anticyclonic anomaly over the Northeast Asia, the terminal of the Rossby wave train, could also results in more CDF in eastern China; (3) Based on these two independent routes of physical mechanisms from both tropics and ex-tropics, a physics-motivated empirical model is conducted, which shows encouraging independent prediction skill during the ten years of 2004-2013. The results therein are useful references for operational departments on seasonal prediction.