Provision of handwashing facilities and proper practices are essential for preventing fecal-oral and acute respiratory infectious diseases. The aim of this study was to assess availability of handwashing facilities and predictors to students' good hygiene practices in Addis Ababa, Ethiopia. A mixed-methods study design was conducted in schools of Addis Ababa from January to March 2020 in 384 students, 98 school directors, 6 health clubs, and 6 school administrators. Data were collected using pretested interviewer-administered questionnaires, interview guide, and observational checklists. The quantitative data were entered into EPI Info version 7.2.2.6 and analyzed using SPSS 22.0. A bivariable at P < .2 and multivariable logistic regression analysis at P < .05 for quantitative and thematic analysis for qualitative data were used. Handwashing stations were available in 85 (86.7%) of the schools. However, 16 (16.3%) schools had neither water nor soap near the handwashing facilities while 33 (38.8%) of schools had both. There was no high school that had both soap and water. Approximately one-third (135, 35.2%) of students practiced proper handwashing, among which 89 (65.9%) were from private schools. The handwashing practices were significantly associated with gender (AOR = 2.45, 95% CI: (1.66-3.59)), having trained coordinator (AOR = 2.16, 95% CI: (1.32-2.48)) and health education program (AOR = 2.53, 95% CI: (1.73-3.59)), school ownership (AOR = 0.49, 95% CI: (0.33-0.72)), and training (AOR = 1.74, 95% CI: (1.82-3.69)). Water supply interruption, and lack of budget, adequate space, training, health education, maintenance, and coordination were the main barriers that prevent students from practicing proper handwashing. Handwashing facilities and materials provision and good handwashing practices of students were low. Moreover, providing soap and water for handwashing was insufficient to promote good hygiene practices. There should be regular hygiene education, training, maintenance, and better coordination among stakeholders to create a healthy school environment.