AbstractBackgroundKnowledge of the specific dynamics of influenza introduction and spread in university settings is limited.MethodsPersons with acute respiratory illness symptoms received influenza testing by molecular assay during October 6–November 23, 2022. Viral sequencing and phylogenetic analysis were conducted on nasal swab samples from case‐patients. Case–control analysis of a voluntary survey of persons tested was used to identify factors associated with influenza; logistic regression was conducted to calculate odds ratios and 95% CIs. A subset of case‐patients tested during the first month of the outbreak was interviewed to identify sources of introduction and early spread.ResultsAmong 3268 persons tested, 788 (24.1%) tested positive for influenza; 744 (22.8%) were included in the survey analysis. All 380 sequenced specimens were influenza A (H3N2) virus clade 3C.2a1b.2a.2, suggesting rapid transmission. Influenza (OR [95% CI]) was associated with indoor congregate dining (1.43 [1.002–2.03]), attending large gatherings indoors (1.83 [1.26–2.66]) or outdoors (2.33 [1.64–3.31]), and varied by residence type (apartment with ≥1 roommate: 2.93 [1.21–7.11], residence hall room alone: 4.18 [1.31–13.31], or with roommate: 6.09 [2.46–15.06], or fraternity/sorority house: 15.13 [4.30–53.21], all compared with single‐dwelling apartment). Odds of influenza were lower among persons who left campus for ≥1 day during the week before their influenza test (0.49 [0.32–0.75]). Almost all early cases reported attending large events.ConclusionsCongregate living and activity settings on university campuses can lead to rapid spread of influenza following introduction. Isolating following a positive influenza test or administering antiviral medications to exposed persons may help mitigate outbreaks.