Background In Egypt, many pesticides are used to control pests in agricultural farms. Our study aimed to investigate knowledge and behaviors of farmers related to pesticide use and their relation to educational level and health locus of control. Health locus of control is the degree to which individuals believe that their health is controlled by internal or external factors. Methods A cross-sectional randomized approach was used to collect data from 335 farmers in Mahmoudiya region, Egypt using an interview questionnaire. Results were analyzed using Pearson Chi-square test, Fisher's exact test, Student t-test and ANOVA. Results The average age of farmers was 34 years and 61% of them didn't receive school education. School education was related to higher levels of knowledge and behaviors. Farmers who received school education had more knowledge about the negative effects of pesticides on health and routes of contamination with pesticides. They also had higher scores on reading labels of pesticides containers and taking precautions after coming in contact with pesticides. Regarding health locus of control, higher internal beliefs were significantly related to higher knowledge and behaviors scores, while there was no significant relation between chance and powerful others beliefs with knowledge or behaviors. Conclusion In the present study, higher level of education and lower level of internal beliefs were related to better knowledge and safer use of pesticides among Egyptian farmers. We recommend that strategies for raising internal beliefs must be included in health education programs that aim to ameliorate pesticides use among farmers.