Despite of public health measures, Hong Kong has experienced four epidemic waves of COVID-19, resulting in 11,468 infected cases and 205 deaths as of March 2021. Our team has established Nanopore MinION and Illumina Miseq platform for whole-genome sequencing of SARS-CoV-2 during the early stage of the pandemic (in February 2020). Phylogenomic analysis enabled us to identify an asymptomatic patient as the source of the first superspreading event of COVID-19 (Buddhist worship hall cluster) happened in late February 2020. After months of relative quiescence, a large COVID-19 outbreak (third wave) occurred in Hong Kong in July 2020. The phylogeny of some early cases indicated that the outbreak was attributed to a single lineage B.1.1.63 (GISAID Clade GR), which was identical to viral genomes isolated from marine crew and aircrew who were exempted from mandatory quarantine. In early October 2020, we identified a novel viral genome (lineage B.1.36.27 GISAID Clade GH) among local cases, which was most closely related to imported cases from Nepal. Based on the genomic evidence, the Hong Kong government has stepped up measures to prevent transmission of SARS-CoV-2 from imported cases, particularly the number of individuals that can be exempted from mandatory quarantine is reduced, and all incoming travellers must be quarantined at designated hotels for 21 days. Continued genomic surveillance of locally-acquired cases is pivotal in detecting novel lineages that enters Hong Kong.