Background: Despite the availability of prophylactic antibiotics prior to skin incisions, surgical site infection (SSI) following cesarean section (CS) remains an unresolved health issue. As a result, this study aimed to assess the incidence and predictors of SSI after a CS. Methods: The authors conducted a prospective cohort study in eastern Ethiopia. The women were serially enrolled until the desired sample size was reached. A structured questionnaire was used to collect data. Women were followed at the hospital during their weekly visits. Culture-based microbiological methods were used to identify causal agents. A binary logistic regression model was used to identify the predictors of SSI after CS. Results: Among serially enrolled women, 336 were followed for 30 days. The incidence of SSI was 7.74% (95% CI: 7.68–7.80). Rupture of the membrane before operation [adjusted odds ratio (AOR)=3.75, 95% CI: 1.85–16.6], labor duration greater than 24 h (AOR=4.04, 95% CI: 1.52–10.79), and postoperative hemoglobin less than 11 g/dl (AOR=3.42, 95% CI: 1.32–8.87) were all significantly associated with SSI. The most common isolated pathogen was Staphylococcus aureus , followed by Escherichia coli . Conclusions: Nearly one-tenth of the women developed SSIs. Factors such as rupture of the membrane before the operation, absence of antenatal care, labor duration greater than 24 h, a midline skin incision, and postoperative hemoglobin less than 11 g/dl were the predictors of SSI. To reduce the incidence of SSI, policymakers should consider the importance of high-quality antenatal care, shorten the duration of labor, and maintain women’s hemodynamics in future SSI prevention bundles.