Previous studies demonstrated that plasma neurofilament light chain (NFL) played important predictive roles in disease progression and neurodegeneration in the preclinical phase of familial Alzheimer’s disease (AD). However, whether plasma NFL has the same predictive roles in sporadic AD is still unclear. In this study, 243 cognitively normal (CN) participants from the ADNI database were divided into two subgroups (CN- and CN+) according to CSF Aβ or AV45-PET. Associations of baseline plasma NFL concentrations or rate of change in plasma NFL with longitudinal data on other biomarkers were tested by multivariate linear mixed effects models (LMEMs). Results showed that plasma NFL concentration and its rate of change were already abnormally high in the preclinical phase of AD. Plasma NFL was associated with three core AD-related biomarkers in preclinical phase. Baseline plasma NFL, but not its rate of change, played predictive roles in both cognitive decline (β = -0.0349, p = 0.0274) and hippocampal atrophy (β = -0.0351, p = 0.0088), especially for preclinical AD participants. In summary, these results indicated that baseline plasma NFL, but not its rate of change, may be a valuable noninvasive tool to assess neurodegeneration and predict longitudinal disease progression in preclinical AD individuals.