Electro-dewatered sludge (EDS) can be bio-dried alone, instead of adding bulking agents. The initial moisture content (IMC) and particle size of the electro-dewatered sludge affect the efficiency and energy consumption during the bio-drying process. This study aimed to investigate the synergistic effects of sludge IMC and particle size on the drying rate and heat production of bio-drying with EDS. Experiments were conducted with two different IMC sludge and two different sludge particle sizes. Results showed that the highest moisture removal rate was 43.18% in treatment T4, which had materials with a smaller particle size (<3 mm) and lower IMC (38.69%). And bio-drying of T4 had the highest biological heat production (7413.14 kJ, i.e., 741.31 kJ/kg sludge), and the lowest bio-drying index (the ratio of water loss to volatile solid loss) was 7.10 among the four treatments. Five thin-layer drying kinetic models and a nonlinear regression method were analyzed to estimate the bio-drying kinetic parameters. The Midilli et al. model had a better fitting result, and the highest R2 value was 0.9929 during bio-drying of EDS. The new coefficients k (0.1465) and n (1.0898) were obtained. Through the heat balance, the heat used for evaporation was 40–57% of the total energy consumption (5873–9140 kJ). According to the PCA, the particle size had a great influence on the bio-drying process. Also, the particle size positively correlated with temperature, moisture ratio, and drying rate.