Abstract Introduction Objectively‐defined subtle cognitive decline (Obj‐SCD) and plasma phosphorylated‐tau181 (p‐tau181) are promising early Alzheimer's disease (AD) markers. However, associations between Obj‐SCD and p‐tau181, and their combined prognostic potential, are unknown. Methods Baseline and 4‐year longitudinal p‐tau181 changes were compared across cognitively unimpaired (CU; n = 402), Obj‐SCD ( n = 199), and mild cognitive impairment (MCI; n = 346) groups. CU and Obj‐SCD participants were further classified as p‐tau181‐positive or negative. Results CU and Obj‐SCD has lower baseline p‐tau181 than MCI and did not differ from one another. Longitudinally, Obj‐SCD had the steepest p‐tau181 increase. Obj‐SCD/p‐tau181‐positive participants had the fastest rates of amyloid accumulation, cognitive decline, and functional decline. Conclusions Despite assumptions that cognitive changes invariably follow biomarker changes, early neuropsychological difficulties may emerge before/concurrently with plasma p‐tau181 changes. Combining Obj‐SCD and p‐tau181, two potentially accessible early markers, was associated with the faster declines in AD‐related outcomes.