Background Pneumonia causes about two million under-five deaths each year, accounting for nearly one in five child deaths globally. Knowing the determinants of under-five pneumonia is useful for prevention and intervention programs that are aimed to control the disease. Thus, the main aim of this study was to assess the determinants of under-five pneumonia at Gondar University Hospital, Ethiopia. Methods An institution-based unmatched case-control study was carried out from April 1 to April 30, 2015, taking a sample size of 435 study participants (145 cases and 290 controls). The researchers used a systematic random sampling technique for selecting cases and controls. Data were entered and cleaned using Epi Info version 7 and exported to SPSS version 20 for analysis. Bivariable analysis was performed, and variables with a p value less than 0.2 were entered into multivariable logistic regression. Determinant factors were identified based on p value less than 0.05 and adjusted odds ratio with 95% confidence interval (AOR with 95% CI). Results An increased odds of pneumonia was associated with children who had diarrhea in the past fifteen days of data collection (AOR = 6.183; 95% CI: 3.482, 10.977), children's mothers who did not hear about how to handle domestic smoking (AOR = 5.814; 95% CI: 2.757, 12.261), and children of mothers who did not follow proper handwashing practice (AOR = 3.469; 95% CI: 1.753, 6.863). Conclusions Being infected with diarrhea, not knowing how to handle domestic smoking, and poor compliance with proper handwashing practice were identified as determinants of pneumonia. Dedicated, coordinated, and integrated intervention needs to be taken to enhance proper handwashing practice by mothers/caregivers, improve the indoor air quality, and prevent diarrheal diseases at the community level.