(1) Background: To assess and compare the temporal trends in the incidence, characteristics and hospital outcomes among children with and without asthma who were hospitalized with anaphylaxis in Spain from 2016 to 2021, and identify the variables associated with severe anaphylaxis among children with asthma. (2) Methods: An observational, retrospective study was conducted using a population-based database. The study population included pediatric patients with anaphylaxis. This population was stratified based on whether they had asthma. (3) Results: The number of hospital admissions was stable from 2016 to 2019, dropping in 2020 and raising to the highest number in 2021. A total of 60.63% of hospitalizations occurred in boys and the most common anaphylactic reactions were due to food consumption (67.28%), increasing over time. The in-hospital mortality (IHM) remained stable and under 1% in all the years studied. The incidence of anaphylaxis was 2.14 times higher in children with asthma than in those without asthma (IRR 2.14; 95% CI 1.87-2.44). Furthermore, it was 1.79 times higher in boys with asthma than in those without asthma (IRR 1.79; 95% CI 1.06-2.45) and 2.68 times higher in girls with asthma than in those without asthma (IRR 2.68; 95% CI 2.23-3.12). Asthma was not associated with severe anaphylaxis (OR 1.31; 95% CI 0.88-1.96). (4) Conclusions: The number of hospitalizations for anaphylaxis in children remained stable from 2016 to 2019, dropping in 2020 and recovering in 2021. IHM was low and remained stable during the study period. The incidence of hospitalizations for anaphylaxis was higher in asthmatic children than in non-asthmatics, but there were no differences in the occurrence of severe anaphylaxis among them.