Ghana adopted the WHO-recommended Seasonal Malaria Chemoprevention (SMC) in 2016 following a pilot study as a vital strategy for malaria control. SMC is the intermittent administration of a preventive and curative dose of anti-malarial medicine (Sulfadoxine-Pyrimetamine + Amodiaquine) during four months of the malaria season. This study monitored the implementation of SMC to ensure the intervention is achieving its target.This was a longitudinal study in four administrative districts of the Upper East Region of Ghana. Children aged between 3 and 59 months were sampled and followed up one week after each cycle of SMC dosing to complete a questionnaire. SMC status was determined through the caregiver's report and child welfare cards, if available. Caregivers were asked if the participant had been treated for malaria since the last cycle. Simple and multiple logistic regressions were employed to determine associations between SMC adherence and the independent variables, with all results interpreted at a 95% confidence level (CI).This study reported an average SMC coverage of 87% (CI: 86.7-89.5) per cycle with a 2% dropout after the first cycle. SMC adherence rate remained above 82% (CI: 1.4-2.5), with malaria incidence decreasing in those who received all four doses of SMC compared to partial recipients. Health system/programme (49%) and patient related factors (33%) were the main reasons reported for non-adherence. Significant predictors of adherence were household size (aOR = 1.04, 95% CI 1.01-1.08), sleeping under bed nets (aOR = 1.88, 95% CI 1.44-2.48), and indoor residual spraying (IRS) presence (aOR = 0.83, 95% CI 0.69-1.99).Despite achieving an average coverage of 87% per cycle, it falls short of the national target of 90%. Notable reasons for drop-outs and non-adherence were, the caregiver being unavailable during the distribution, highlighting the need for diversified approaches in SMC campaigns to enhance coverage, and adherence, and maximize intervention benefits.