Background: Preconception care has the potential to reduce maternal and child morbidities and mortalities. It is a window of opportunity to timely alter or eliminate risk factors for adverse pregnancy outcomes. However, despite strong evidence on the effectiveness of preconception care in safeguarding maternal and child health, its uptake remains low. Therefore, this study aimed to explore barriers to the uptake of preconception care. Methods: A descriptive qualitative study was conducted in Mana district, Jimma Zone, Oromia region, Southwest Ethiopia from March 02 to April 10, 2019. A purposive sampling approach was used, and 13 key informant interviews (6 in rural and 7 in urban areas) were held with women of different age groups, health extension workers, and health care providers of different professions. In addition, 4 focused group discussions with women of reproductive age groups (two with rural women only and two with urban women only) were conducted. The data were collected by trained experts using semi-structured guides. An inductive process of thematic analysis was employed and the data were coded, categorized, and thematized using Atlas ti version 7.0.71 software. Results: Four women of reproductive age groups, 1 older woman (grandmother), 2 health extension workers, and 6 health care providers of different professions were interviewed. In addition, a total of 38 women of reproductive age groups participated in the 4 focused group discussions: 20 in the two rural-focused group discussions and 18 in the two urban-focused group discussions. The findings indicated the presence of many barriers affecting the uptake of preconception care and organized into five themes: women-related barriers, husband-related barriers, community-related barriers, health-service-related barriers, and media-related barriers.