Abstract Background: Open defecation remains a major public health challenge in Ghana and across sub-Saharan Africa, with persistent rural-urban inequalities undermining progress toward Sustainable Development Goal 6.2 (SDG 6.2). Despite two decades of national sanitation programming, structural and equity barriers continue to constrain progress. A repeated cross sectional analyses and longitudinal analysis combining WHO-standardised inequality measures, temporal trend modelling, and projections remain absent from the literature for Ghana. Methods: National, rural, and urban open defecation prevalence (2000-2024) was analysed using WHO Health Equity Assessment Toolkit (HEAT) data. Four inequality measures: Difference, Ratio, Population Attributable Risk (PAR), and Population Attributable Fraction (PAF), quantified rural-urban disparities. Joinpoint regression identified statistically significant trend inflection points across MDG and SDG eras. ARIMA models projected prevalence to 2030 under status quo, accelerated, and decelerated scenarios; hold-out validation confirmed high forecast accuracy across all series (MAPE