The emergence of SARS-CoV-2 variants with enhanced transmissibility and partial immune escape (also known as Variants of Concern, VOC) has characterised the second year of the COVID-19 pandemic. Genomic surveillance allows identifying hidden, fast-spreading lineages and VOCs before they become a public health threat. The Chilean Public Health Institute (Instituto de Salud Pública, ISP) has led SARS-CoV-2 genomic surveillance initiatives in Chile. Using sequencing data, the ISP has signalled the introduction of VOCs and characterised their transmissibility and mutational signatures, contributing to a better understanding of the local features of the pandemic.