Artificial shale ceramsite, a lightweight aggregate, has been widely used in construction field. However, it can lessen concrete's mechanical properties due to its porous inner-structure. In this study, nano-silica (NS) and fly ash (FA) was adopted to improve the mechanical performance and durability of internal-cured concrete containing artificial shale ceramsite (ASC-ICC). The synergistic effects of NS and FA on ASC-ICC was assessed by performing hydration degree, mechanical properties, durability under combined sulfate and drying-wetting attack, SEM-EDS and XRD investigations. Results show that incorporating NS and FA has a positive synergistic effect when the dosage of NS and FA is less than 2.5 and 20 wt%, respectively. When the amount of FA increases to 40 wt%, both mechanical properties and durability of ASC-ICC suffer a significant decrease given that the loose microstructure due to insufficient early-age hydration provides more channels for sulfate ions to access the inner concrete. The enhancing effect of NS is improved by the internal curing of ASC since more calcium hydroxide can be produced to participate in the pozzolanic reaction with NS. Mixture C1F2 exhibits the best performance given an increase of 64.29% and 16.26% in the compressive and flexural strength (compared to mixture C0F1) and an increase of 6.46% in the flexural strength (in comparison to the initial value) even after 49 attack cycles (i.e., 294 d), which indicates that the combination of 1.0 wt% NS and 20 wt% FA is most conducive to improving ASC-ICC performance.