Background: Surgical site infection is the third most commonly reported nosocomial infection. Different primary studies on Surgical site infection (SSI) were conducted in Ethiopia. However, variation among those studies was seen. This study was aimed to estimate the national prevalence of SSI, its bacterial profile and associated factors of SSI in Ethiopia. Methods: PubMed, Cochrane library, and Google Scholar were searched. A funnel plot and Egger’s regression test were used to see publication bias. I-squared statistic was applied to check heterogeneity of studies. A weighted inverse variance random-effects model was applied to estimate the national prevalence of SSI, its bacterial profile and the effect size of associated factors. The subgroup analysis was conducted by region, study design, and year of study conducted. Result: A total of 18 studies were used for prevalence of SSI, its bacterial profile and associated factors. The pooled prevalence of SSI was 11.58 (95% CI 9.78, 13.38). The pooled prevalence of culture positive SSI infection among patients who develop clinical sign and symptoms of SSI was also 80.42% (95% CI 70.86, 89.99). SSI was majorly caused by S. aureus (28.47%) and E. coli (15.93%). Drinking an alcohol (AOR = 6.28; 95%CI: 2.9–13.3); women’s having chorioaminities (AOR = 8.67; 95%CI: 4.63–16.27); patients living in rural areas (AOR = 3.10; 95%CI: 1.57–6.14); patients who undergo previous surgery (AOR = 3.94; 95%CI: 1.7–7.17) and women’s who had rupture of membrane >12 hour (AOR=5.29; 95%CI: 2.73–10.25) were identified factors of SSI. Conclusions: The prevalence of SSI in Ethiopia was high. This indicates calling for the need of better allocating resources and implementing a program for controlling Surgical site infections in Ethiopia.