We show that a CP-violating interaction induced by a derivative coupling between the running vacuum and a non-conserving baryon current may dynamically break CPT and trigger baryogenesis through an effective chemical potential. By assuming a non-singular class of running vacuum cosmologies which provides a complete cosmic history (from an early inflationary de Sitter stage to the present day quasi-de Sitter acceleration), it is found that an acceptable baryon asymmetry is generated for many different choices of the model parameters. It is interesting that the same ingredient (running vacuum energy density) addresses several open cosmological questions/problems: avoids the initial singularity, provides a smooth exit for primordial inflation, alleviates both the coincidence and the cosmological constant problems, and, finally, is also capable of explaining the generation of matter-antimatter asymmetry in the very early Universe.