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Background Testing and contact tracing (CT) can interrupt transmission chains of SARS-CoV-2. Whole-genome sequencing (WGS) can potentially strengthen these investigations and provide insights on transmission. Methods We included all laboratory-confirmed COVID-19 cases diagnosed between 4 June and 26 July 2021, in a Swiss canton. We defined CT clusters based on epidemiological links reported in the CT data and genomic clusters as sequences with no single-nucleotide polymorphism (SNP) differences between any 2 pairs of sequences being compared. We assessed the agreement between CT clusters and genomic clusters. Results Of 359 COVID-19 cases, 213 were sequenced. Overall, agreement between CT and genomic clusters was low (Cohen's κ = 0.13). Of 24 CT clusters with ≥2 sequenced samples, 9 (37.5%) were also linked based on genomic sequencing but in 4 of these, WGS found additional cases in other CT clusters. Household was most often reported source of infection (n = 101 [28.1%]) and home addresses coincided well with CT clusters: In 44 of 54 CT clusters containing ≥2 cases (81.5%), all cases in the cluster had the same reported home address. However, only a quarter of household transmission was confirmed by WGS (6 of 26 genomic clusters [23.1%]). A sensitivity analysis using ≤1-SNP differences to define genomic clusters resulted in similar results. Conclusions WGS data supplemented epidemiological CT data, supported the detection of potential additional clusters missed by CT, and identified misclassified transmissions and sources of infection. Household transmission was overestimated by CT.