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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic surveillance is crucial for understanding viral evolution and guiding public health responses. However, many countries, particularly in Central America, have limited sequencing capacity, resulting in scarce and delayed data. This study addresses this gap by analyzing 320 SARS-CoV-2 genomes sequenced from a major diagnostic center in Guatemala City, Guatemala, between April and August 2021. Clade 21J (Delta) was predominant (46.2%), followed by 19B (29.4%) and 20J (Gamma, 6.6%). The most reported symptoms were cough, headache, malaise, and myalgia/arthralgia. Among patients infected with the Delta variant, 39.9% reported being contacts from a confirmed case, less than reported by the patients infected with non-Delta variants (53.2%, p= 0.017). The proportion of signs and symptoms was similar among these two groups, except for the history of fever which was increased ~2-fold in the Delta group. This research contributes valuable genomic and epidemiological data to elucidate SARS-CoV-2 variant dynamics in Central America and emphasizes the importance of global genomic surveillance for pandemic preparedness and response.