In order to minimize the degradation of encapsulated compounds in the harsh environment of release medium and to minimize bursting release, a model drug was encapsulated in a kernel of ultrafine cellulose acetate (CA) and gelatin (GL) blend fibers via coaxial electrospinning. The effects of the GL ratio on the properties of the shell solution were investigated, along with the core-to-shell ratio. Transmission electron microscopy images showed that core-shell coaxial fibers were fabricated successfully. Scanning electron microscopy images showed that the average diameter of the fibers was 913 6 180 nm. As the GL ratio was increased, the viscosity of the shell solution decreased. In addition, more pronounced shear thinning occurred, which resulted in coaxial fibers with thinner shells. Release characteristics of the encapsulated amoxicillin in pepsin-containing simulated gastric fluid (SGF) with a pH of 1.2 were also investigated. It showed that the release of amoxicillin occurs owing to Fickian diffusion mechanism, with the release half-time being approximately 5 h. Bursting release was not observed, and fibers exposed to the SGF remained intact even after 24 h. These core-shell fibers should be suitable for applications requiring the sustained release of compounds in the gastrointestinal tract.