During 2020, Coronavirus Disease-19 (COVID-19) incidence fluctuated in two clear waves across the spring and autumn periods. This study was designed to compare the maternal and perinatal clinical outcomes in obstetrics patients with COVID-19 between the two waves of infection in Spain. We conducted an observational, analytical, ambispective cohort study with longitudinal follow-up of mothers with confirmed SARV-CoV-2 infection from different hospitals in our country between March–November 2020. We recruited 1295 pregnant women with SARS-CoV2 infection from 78 hospitals, 846 (65.3%) of whom were diagnosed during the first wave and 449 (34.7%) during the second wave. Our results show that patients developing COVID-19 during the first wave had more symptoms at triage, early in pregnancy with greater rates of COVID-19-related maternal morbidity; caesarean section and preterm birth in the first wave. We register two cases of maternal mortality and only during the first wave. Maternal morbidity events showed a strong link to perinatal mortality events in the first wave compared to the second wave, in which maternal morbidity was more associated with pneumonia. Likewise, maternal morbidity showed a strong correlation with perinatal morbidity events in both waves. We describe the differences between the patients’ profiles and management between the two waves and related to maternal and perinatal outcomes. Differences were also observed in the management of pregnant women with COVID-19. Thus, there were fewer caesarean sections, and maternal and perinatal morbidity events were reduced in the second wave, while the impacts of respiratory symptoms and their severity, including a greater need for maternal treatment, were greater in this last period. Identifying the impact that changes in the profile as well as in the treatment have on maternal–perinatal morbidity and mortality will help improve the well-being of our patients and their newborns.