Background: Male involvement during antenatal care is an influential strategy for improving maternal health service utilization, especially institutional delivery. In Ethiopia, only one-fifth of pregnant women were accompanied to antenatal care. It is among those neglected issues, as it is not well studied, specifically determinant factors of male involvement during antenatal care are not known. Objective: This study aimed to identify the determinants of male partner involvement during antenatal care among pregnant women in Gedeo Zone, South Ethiopia. Methods: Community based unmatched case-control study was carried out from January to March 2019 among 804 (cases-402 and controls-402) selected pregnant women having antenatal follow up in Gedeo zone by stratified sampling technique. Data was collected using a pretested, structured, interviewer-administered questionnaire. A survey was conducted in the 22 selected kebeles in the Gedeo zone to identify cases and control. The data was entered using Epi-data and exported to SPSS (Statistical Package for Social Sciences) for analysis. Descriptive analysis like frequency, percentage, rates, and inferential analysis such as binary logistic regression are used. Statistical significance is declared at α < 0.05. The result is presented using text and tables. Results: Husband and maternal age difference (AOR = 1.12, 95% CI [1.06, 1.18]), maternal age at marriage (AOR = 0.86, 95% CI[0.81,0.93]), women empowerment (AOR = 0.20, 95% CI[0.13, 0.30]), type of nearby health facility (AOR = 4.94, 95% CI[1.67, 14.60]) and provider invitation of male partner to antenatal care examination room (AOR = 0.32, 95% CI[0.20, 0.51]) were determinants of male partner involvement during antenatal care.