Abstract Background Vaccine refusal remains a major challenge to polio eradication in Afghanistan, one of the two remaining countries endemic for wild poliovirus type 1. Understanding the factors influencing vaccine refusal is essential for designing effective interventions to improve vaccination uptake. Methods A descriptive cross-sectional study was conducted in 2024 among 698 caregivers or household decision-makers from families that refused polio vaccination in Kabul, Kunduz, Faryab, and Jawzjan provinces. Participants were selected from refusal household lists maintained by the Expanded Programme on Immunization (EPI). Data were collected using a structured questionnaire assessing sociodemographic characteristics, routine immunization status, knowledge of poliomyelitis and polio vaccination, and reasons for vaccine refusal. Descriptive statistics were used to summarize the findings. Results Among the 698 respondents, 62.2% were male and 65.5% were aged 21–40 years. A total of 1,658 children were identified, of whom 89.8% had not received polio vaccination despite 97.6% of households reporting visits by house-to-house vaccination teams. Routine immunization coverage was low among refusal households, with overall coverage ranging from 40% to 48% across vaccine antigens. Although 57.3% of respondents reported knowledge of poliomyelitis and 71.3% were aware of the polio vaccine, only 38.1% believed that vaccination was useful for disease prevention. The most common reasons for vaccine refusal were family opposition (41.8%), vaccine mistrust (34.2%), religious concerns (31.4%), safety concerns (27.8%), fear of side effects (27.5%), and perceived vaccine ineffectiveness (25.8%). Misconceptions regarding infertility, immune-system effects, premature puberty, and illness following vaccination were also frequently reported. Access-related barriers were uncommon (6.3%). Conclusion Polio vaccine refusal in Afghanistan is driven primarily by family decision-making, mistrust, religious concerns, safety perceptions, and misinformation rather than access to vaccination services. Strengthening community engagement, risk communication, and trust-building initiatives while addressing misconceptions through culturally appropriate interventions may improve vaccine acceptance and support polio eradication efforts.