Background Healthcare practitioners (HCPs) are at high risk of influenza. Seasonal influenza vaccines can reduce influenza-associated morbidity in healthcare settings, but despite mandatory influenza vaccination in the Kingdom of Saudi Arabia, the vaccination uptake rate among HCPs is below expectations. This study investigated vaccination trends from 2017 to 2020 to identify factors affecting vaccination among HCPs during the COVID-19 pandemic flu and subsequent seasons. Methods Cross-sectional study among HCPs was conducted in January 2021. A structured questionnaire was shared via social media. Vaccine uptake predictors were identified using descriptive statistics and logistic regression models (p-value 0.05). Results A total of 424 HCPs (118 physicians and 306 nurses) completed the questionnaire. Vaccine uptake increased from 2017 to 2019 (45% to 52% to 62%) but fell (to 59%) during the 2020 COVID-19 pandemic flu season. Multivariable analysis indicated participants >40 years old (AOR 3.09, 95% CI 1.64–5.83), female (AOR 1.74, 95% CI 1.13–2.67), non-Saudi (AOR 2.62, 95% CI 1.72–4.01), nurses (AOR 2.70, 95% CI 1.75–4.17), and who possessed accurate knowledge of the flu vaccine efficacy duration (AOR 3.04, 95% CI 1.87–4.94) were more likely to have received the vaccine. However, 79% of HCPs declared their intention to be vaccinated in the 2021 flu season, with participants >40 years old, female (AOR 2.25, 95% CI 1.38–3.68), non-Saudi (AOR 3.79, 95% CI 2.34–6.16), or nurses (AOR 2.94, 95% CI 1.82–4.76) more likely to do so. Conclusion Influenza vaccination uptake declined among HCPs during the 2020 flu season compared with the previous season but is expected to increase in the upcoming 2021 season. Nevertheless, the findings are encouraging and indicate increased willingness of HCPs to become vaccinated in the upcoming 2021 season, but coverage could be further increased by policymakers via a comprehensive plan focusing particularly on younger HCPs, Saudis, males, and physicians.