The impact of SARS-CoV-2 variants on maternal and neonatal outcomes during pregnancy is still poorly understood, and the emergence of different variants has further complicated our understanding of the virus’s effects. This retrospective, monocentric study aimed to fill this knowledge gap by analyzing the outcomes of pregnant women with acute SARS-CoV-2 infection caused by the Alpha, Delta, and Omicron variants. The study, conducted between December 2020 and March 2022 at San Marco Hospital, included 313 pregnant women with confirmed SARS-CoV-2 infection. The results showed that the Delta variant was associated with a significantly higher incidence of adverse outcomes, such as premature births, maternal intensive care unit admission, intrauterine growth restriction, and small for gestational age infants. Additionally, the Delta variant was linked to lower Apgar scores, higher maternal and fetal mortality rates, and increased levels of various biomarkers indicating more severe illness. Finally, the Delta variant also presented a greater possibility of vertical transmission. These findings underscore the complexity of understanding the impact of SARS-CoV-2 on pregnancy outcomes, especially considering the distinctive characteristics of different variants. By better understanding the specific impacts of each variant, appropriate preventive measures and management strategies can be implemented to optimize maternal and neonatal outcomes.