Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island’s population and became a critical threat to public health. We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Our analyses revealed that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after approximately 4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated circulation in Puerto Rico from September to December 2020 and subsequently spread to the United States. The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses.