Guillain–Barré syndrome (GBS) is an acute autoimmune polyneuropathy with substantial geographic variations in demography, antecedent events, clinical manifestations, electrophysiological sub-types, diagnostic findings, treatment modalities, and prognostic indicators. However, there is limited contemporary data on GBS patient profiles and prognostic factors from low-resource settings like Ethiopia. The objective of this study is to investigate the clinical profile, factors associated with mortality, and hospital outcomes among GBS patients admitted to Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. A retrospective cross-sectional study was conducted among 60 GBS patients admitted to TASH from January 2018 to December 2022. Data on demographics, clinical features, treatments, complications, and outcomes were extracted from medical records. Bivariate and multivariate logistic regression analyses identified factors associated with mortality and poor hospital outcomes. The cohort had a mean age of 28.5 years, with 76.7% aged 14–34 years. Males comprised 61.7% of cases. Ascending paralysis (76.7%) was the predominant presentation. Absent or reduced reflexes were seen in 91.7% of patients. The most common antecedent event was gastroenteritis (26.7%), followed by upper respiratory tract infection (URTI) (15%) and vaccination (11.7%). The mean interval from symptom onset to hospital presentation was 8.77 days, and the peak symptom severity was 4.47 days. The axonal variant (75.5%) was the most common subtype, followed by the demyelinating variant (24.5%). Intravenous immunoglobulin was administered to 41.7% of patients. Respiratory failure requiring invasive mechanical ventilator (MV) support occurred in 26.7% of cases. The mortality rate was 10%, with mechanical ventilation being the only factor significantly associated with mortality (95% CI 2.067–184.858; P < 0.010). At discharge, 55% had a good outcome, and 45% had a poor outcome, according to the Hughes Functional Disability Scale (HFDS). Mechanical ventilation (AOR 0.024, 95% CI 0.001–0.607) and a GBS disability score > 3 (AOR 0.106, 95% CI 0.024–0.467) were factors significantly associated with poor hospital outcomes. GBS in this cohort primarily affected individuals of young age, commonly preceded by gastroenteritis and characterized by a high frequency of the axonal variant. Mechanical ventilation was found to be significantly linked to mortality. Alongside mechanical ventilation requirements, severe disability upon presentation emerged as a crucial determinant of poor outcomes upon discharge, underscoring the importance of early identification of high-risk patients and prompt interventions.