The advantageous location, port clusters, strong economic strength, developed financial system, rational and orderly urban division of labor and modern industrial system of Guangdong-Hong Kong-Macao greater bay area provide sustainable driving force for innovation activities in this region. This paper selected the Gini-coefficient, first degree index and concentration index to measure the spatial pattern characteristics of innovation output in Guangdong-Hong Kong-Macao greater bay area. The results show that the innovation output presented a spatial pattern of center-periphery in the study region with Shenzhen and Guangzhou as the dual centers and engines of innovation and Dongguan and Foshan as the main innovative areas. Further empirical analysis of the impact of various factors on innovation output in the study region found that R&D expenditure, the number of R&D personnel, the level of economic development and industrial structure all have significant promoting effects on innovation output. Accordingly, this paper put forward countermeasures and suggestions to promote the innovative development of Guangdong-Hong Kong-Macao greater bay area and build a world-class scientific and technological innovation bay area.