This study was designed to evaluate the effects of yacon (Smallanthus sonchifolius) juice byproduct (YJB) on the growth performance, digestive and antioxidant enzyme activities, and disease resistance against Streptococcus iniae of juvenile black rockfish (Sebastes schlegelii) based on different feeding schedules. Four different YJB feeding strategies were evaluated: feeding the fish a basal diet continuously (control, T0), feeding them YJB (2.5 g/kg) continuously (T1), feeding them YJB for 1 day and the basal diet the next day (T2), and feeding them YJB for 1 day and the basal diet for the following 2 days (T3). No difference in survival among the treatments was found after the 8-week feeding trial (p > 0.05). However, the T1 and T2 groups exhibited significant enhancements in final body weight, weight gain, and specific growth rate compared with the T0 and T3 groups. Furthermore, the T1 and T2 groups showed a significant improvement in feed consumption, feed efficiency, and protein efficiency ratio compared with the T0 and T3 groups. No significant differences in the condition factor or viscerosomatic and hepatosomatic indices were observed among all the groups. Intestinal amylase, trypsin, and lipase activity was significantly (p < 0.05) higher in the T1 and T2 groups than in the T0 and T3 groups. Lysozyme, superoxide dismutase, and catalase activity along with glutathione peroxidase content were significantly (p < 0.05) higher under all YJB feeding regimens than those under the control treatment. The survival rates in all the YJB treatment groups after the S. iniae challenge were significantly (p < 0.05) enhanced. In conclusion, we recommend offering YJB at day-to-day intervals to improve growth performance, digestive enzyme activity, antioxidant status, and disease resistance against S. iniae.