The epidemic has rapidly spread across China since the outbreak of the novel coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province in December 2019. Urban agglomerations are not only the main spatial organization forms of China's new urbanization but also interconnected urban networks that gather a considerable number of cities of different natures, types, and scales. Urban agglomerations with relatively high degrees of economic development, large population densities, and developed transportation are key regions associated with the spread of the epidemic. In these regions, cross-regional infection risk is high, and joint prevention and control is difficult. This article takes the urban agglomerations in the epidemic-intensive area as its research object. It focuses on the key urban agglomerations through kernel density analysis; measures the number, population migration, and spatial distribution of the epidemic from multi-spatial scales; uses spatial autocorrelation to analyze the distribution characteristics of the epidemic; and uses the geographic detector method to objectively measure the leading factors of the epidemic in urban agglomerations. The aim of these analyses is to excavate the relevant dominant factors from the landscape pattern to provide scientific basis and ideas for ecological and safe spatial planning and governance. Results show that ① the high-kernel density areas of the number of infection cases nationwide is spatially coupled with the four urban agglomerations. The number of confirmed cases in the first core city accounts for a high proportion in the urban agglomerations, and the spread and distribution of the epidemic typically radiates outward from the core city. The outflow of people in Hubei has a certain impact on the epidemic situation in the inflowing area. ② There are significant spatial agglomeration characteristics in the number of infection cases and the growth rate of infections nationwide. The spatial agglomeration of the number of infections within the urban agglomerations has gradually weakened from the Middle Yangtze urban agglomeration to other urban agglomerations. ③ The geographic detector reveals that the population density, urban and rural construction, transportation, health, science and technology, and ecological green space are the dominant factors in the spread of the epidemic, and the combined effect produced by the intersecting factors can increase the explanatory power. ④ The landscape pattern of ecological and construction land have strong ability to explain the epidemic; aggregation of construction land and extension of ecological land are main factors.