Childbirth self-efficacy has been identified as a significant indicator of a positive childbirth experience. It is, however, the most neglected aspect of maternal care, and evidence in this regard was lacking in Ethiopia. Therefore, this study aimed to assess perceived childbirth self-efficacy and its associated factors among pregnant women in the Gurage zone, southern Ethiopia. The current study was conducted from April to May 2022 using a facility-based cross-sectional study design. We used a systematic sampling technique and selected a total of 423 women. To collect the data, we utilized an interviewer-administered questionnaire containing a childbirth self-efficacy inventory scale. Multiple linear regression analysis was employed to discover the factors influencing a woman's self-efficacy during childbirth. The current study included 423 pregnant women in total. This study revealed that the overall mean score for perceived childbirth self-efficacy was 489.06 (SD = 65.77). Social support (β = 0.214, P< 0.001), psychological well-being (β = 0.254, P< 0.001), education status at the secondary level (β = 0.151, P< 0.001), no fundal pressure (β = 0.11, P = 0.010), and planned pregnancy (β = 0.10, P =0.013) were positively associated with childbirth self-efficacy. Fear of childbirth (β = 0.19, P< 0.001), Primipara women (β = 0.14, P< 0.001), women who had experienced discomfort during vaginal examination (β = 0.10, P = 0.009), and women who experienced the inability to push (β = 0.10, P = 0.013) were negatively associated with childbirth self-efficacy. The overall mean score for the perceived childbirth self-efficacy was high when compared to the previous studies conducted in Australia. Healthcare professionals should create multifaceted strategies to support childbirth self-efficacy, such as relaxation techniques, prenatal psycho-education to reduce childbirth fear, enhance psychological well-being and encourage social support, particularly partner support during pregnancy and childbirth.