Upper-respiratory tract infections (URTI) are the leading causes of childhood morbidities. This study investigated etiologies and patterns of URTI among children in Mwanza, Tanzania. A cross-sectional study involving 339 children was conducted between October-2017 and February-2018. Children with features suggestive of URTI such as nasal congestion, dry cough, painful swallowing and nasal discharge with/without fever were enrolled. Pathogens were detected from nasopharyngeal and ear-swabs by multiplex-PCR and culture respectively. Full blood count and C-reactive protein analysis were also done. The median age was 16 (IQR: 8-34) months. Majority (82.3%) had fever and nasal-congestion (65.5%). Rhinitis (55.9%) was the commonest diagnosis followed by pharyngitis (19.5%). Viruses were isolated in 46% of children, the commonest being Rhinoviruses (23.9%). Nineteen percent of children had more than 2 viruses; Rhinovirus and Enterovirus being the commonest combination. The commonest bacteria isolated from ears were Staphylococcus aureus and Pseudomonas aeruginosa. Children with viral pathogens had significantly right shift of lymphocytes (73%-sensitivity). Majority (257/339) of children were symptoms free on eighth day. Viruses are the commonest cause of URTI with Rhinitis being the common diagnosis. Rapid diagnostic assays for URTI pathogens are urgently needed in low-income countries to reduce unnecessary antibiotic prescriptions which is associated with antibiotic resistance.