Early prediction of aging trajectories of lithium-ion (Li-ion) batteries is critical for cycle life testing, quality control, and battery health management. Although data-driven machine learning (ML) approaches are well suited for this task, unfortunately, relying solely on data is exceedingly time-consuming and resource-intensive, even in accelerated aging with complex aging mechanisms. This challenge is rooted in the highly complex and time-varying degradation mechanisms of Li-ion battery cells. We propose a novel method based on physics-guided machine learning (PGML) to overcome this issue. First, electrode-level physical information is incorporated into the model training process to predict the aging trajectory’s knee point (KP). The relationship between the identified KP and the accelerated aging behavior is then explored, and an aging trajectory prediction algorithm is developed. The prior knowledge of aging mechanisms enables a transfer of valuable physical insights to yield accurate KP predictions with small data and weak correlation feature relationship. Based on a Li[NiCoMn]O 2 cell dataset, we demonstrate that only 14 cells are needed to train a PGML model for achieving a lifetime prediction error of 2.02% using the data of the first 50 cycles. In contrast, at least 100 cells are needed to reach this level of accuracy without the physical insights.