Abstract Background The burden of cervical cancer continues to rise in developing economies. Women in the sub-Saharan African region have higher chances of developing cervical cancer due to a greater prevalence of related risk factors. The purpose of this study was to determine the effect of health education intervention on cervical cancer and screening perceptions of women in the Komenda, Edina, Eguafo, and Abirem (K.E.E.A) District in the Central Region of Ghana. Methods A non-equivalent control-group design was used to select church women; 396 in the intervention group and 386 in the control group, aged 11 to 70 years in the K.E.E.A District in the Central Region of Ghana. Data was collected via a validated structured interview schedule and analysed using the paired - and independent-samples t-tests, Kruskal-Wallis test, and Mann-Whitney U test. Results A comparison of the mean differences between the pre-post-test scores for the intervention and control groups showed a statistically significant difference for knowledge of cervical cancer (t = 6.22, df = 780, p = 0.001), knowledge of cervical cancer screening (t = 5.96, df = 780, p = 0.001), perceived seriousness (t = 3.36, df = 780, p = 0.001), perceived benefits (t = 9.19, df = 780, p = 0.001), and perceived barriers (t = 3.19, df = 780, p = 0.001). However, perceived susceptibility for the intervention group reduced, evidenced by a decrease in the mean (mean = − 0.12) compared to the control group (mean = 0.93) and this was statistically significant (t = 2.72, df = 780, p = 0.007). Conclusions Health education interventions are critical in improving knowledge and perceptions, and increasing self-efficacy of women about cervical cancer and screening. Trial registration ISRCTN Registry: Current Controlled Trials, ISRCTN13468198. Registered 22 March 2019.