As the strategic core regions of national economic development, the urban agglomerations in the eastern coastal area of China has played a critical role in the implementation of innovation-driven development strategy and construction of the innovative country. Based on the dataset of innovation input and output spanning the 2001-2015 period, the SFA method and spatial Durbin model are applied to measure and examine the innovation efficiency and its influencing factors and spatial spillover effect in the five major urban agglomerations. Our results suggest that the innovation efficiency of five major urban agglomerations showed a steady increase over the studied period. Among the five urban agglomerations, the innovation efficiency in the Beijing-Tianjin-Hebei region rises slowly while that of Shandong Peninsula has increased relatively fast. The growth rate and average of innovation efficiency in the Yangtze River Delta fell behind the Shandong Peninsula and Beijing-Tianjin-Hebei region. Meanwhile, innovation efficiency in core cities of urban agglomerations is low, although they have high-input in innovation resources. Moreover, there is a significantly positive spatial spillover effect of innovation efficiency between cities in the five urban agglomerations. Economic development, agglomeration economies, FDI, the quality of labor force, the financial support by government, infrastructure, secondary industrial ratio and high-tech industries have direct and indirect effects on innovation efficiency in the urban agglomerations.