Background Food safety and hygiene are currently a global health apprehension especially in unindustrialized countries as a result of increasing food-borne diseases (FBDs) and accompanying deaths. This study aimed at assessing knowledge, attitude, and hygiene practices (KAP) of food safety among street-cooked food handlers (SCFHs) in North Dayi District, Ghana. Methods This was a descriptive cross-sectional study conducted on 407 SCFHs in North Dayi District, Ghana. The World Health Organization’s Five Keys to Safer Food for food handlers and a pretested structured questionnaire were adapted for data collection among stationary SCFHs along principal streets. Significant parameters such as educational status, average monthly income, registered SCFHs, and food safety training course were used in bivariate and multivariate logistic regression models to calculate the power of the relationships observed. Results The majority 84.3% of SCFHs were female and 56.0% had not attended a food safety training course. This study showed that 67.3%, 58.2%, and 62.9% of SCFHs had good levels of KAP of food safety, respectively. About 87.2% showed a good attitude of separating uncooked and prepared meal before storage. Good knowledge of food safety was 2 times higher among registered SCFHs compared to unregistered [cOR=1.64, p=0.032]. SCFHs with secondary education were 4 times good at hygiene practices of food safety likened to no education [aOR=4.06, p=0.003]. Above GHc1500 average monthly income earners were 5 times good at hygiene practices of food safety compared to below GHc500 [aOR=4.89, p=0.006]. Registered SCFHs were 8 times good at hygiene practice of food safety compared to unregistered [aOR=7.50, p<0.001]. The odd for good hygiene practice of food safety was 6 times found among SCFHs who had training on food safety courses likened to those who had not [aOR=5.97, p<0.001]. Conclusions Over half of the SCFHs had good levels of KAP of food safety. Registering as SCFH was significantly associated with good knowledge and hygiene practices of food safety. Therefore, our results may present an imperative foundation for design to increase food safety and hygiene practice in the district, region, and beyond.