Introduction <p>Asthma is a common chronic respiratory disorder that affects individuals of all ages and backgrounds. As per our knowledge, few studies has evaluated the knowledge and perception of asthma among adolescents in Nsukka, Enugu State, Nigeria.</p> Objectives <p>The study assessed the knowledge and perception of asthma among secondary school students in Nsukka.</p> Methods <p>This was a cross-sectional study that was conveniently carried out among five (5) private-owned and 5 government-owned secondary schools in Nsukka. Only the senior secondary students (SS1 to SS3) were involved in the study, of which the students belong to either of three specialized classes: Humanities, Sciences, and Business. Students from each of the classes were randomly selected to fill out the questionnaire. Frequencies, percentages, mean and median were used to describe all the variables while Pearson’s Chi-square test, correlation, and multiple regression were used to establish associations, relationships, and predictors respectively among the variables. The statistical significance level was set at <i>p</i> &lt; 0.05. </p> Results <p>A total number of 1840 students participated in the study (mean age = 16.11 ± 1.72&#xa0;years). Most of the students were in science class (73.2%). There was high awareness about asthma (85.5%) and less than half of them had poor asthma knowledge (51.3%) and a poor perception of asthma (54.6%). The mean percentage knowledge score was associated with age [X² (2) = 7.16, p = 0.028] and class [X² (2) = 12.37, p = 0.002] while mean percentage perception score was associated with age [X² (2) = 11.02, p = 0.004] and class [X² (2) = 26.81, p ≤ 0.0001].</p> Conclusion <p>Most of the students knew about asthma while a little more than half of them had poor knowledge and poor perceptions about asthma.</p>