This study aims to evaluate the changes in phenolic acids, lignans and tocopherols of sesame seeds during 0–6 days of germination by monitoring the activities of phenolic metabolism-related enzymes and the expression of key genes in the tocopherol synthesis pathway. Sesamol, which is the most active lignan antioxidant, greatly increased, and most of the phenolic acid contents increased to varying degrees after germination. Correspondingly, the related enzymes, including phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), and 4-coumarate:coenzyme A ligase (4CL), were activated. Germination also promoted the conversion of γ-tocopherol to α-tocopherol with the expression of related genes changed. Additionally, there was a high correlation between the tocopherol content and the relative expression levels of key genes. The germination process also increased the bio-accessibility of lignans and tocopherols. Therefore, germination can be utilized to improve the nutritional value of sesame-related products.