AbstractDengue fever poses a significant global health threat, with over 50 million annual infections spanning more than 100 countries. Given the absence of a specific treatment, medical intervention primarily targets symptom alleviation. The present study utilizes a Caputo-type fractional-order derivative operator to investigate and analyze the dynamics of dengue virus spread within a host with adaptive immune responses. The developed model describes and analyzes the dynamics of immune cells, free dengue particles, infected monocytes, and susceptible monocytes in the presence of cytotoxic T-Lymphocytes. A range of analytical methods is employed to probe the fractional-order within-host model. The application of the generalized mean value theorem aids in investigating the model’s solutions, employing positivity and boundedness theory. Furthermore, the Banach fixed-point approach is utilized to establish the existence and uniqueness of solutions. Employing the normalized forward sensitivity approach, the fractional-order system’s response to various model parameters is scrutinized. The study reveals that the dynamics of the viral model are significantly influenced by the transmission rate and parameters representing adaptive immune responses. Numerical simulations underscore the critical role of transmission rates and adaptive immune responses in the model. Additionally, the study examines the impact of memory on the density of susceptible monocytes, infected monocytes, free dengue particles, and immune cells to optimize immune responses. Through simulations, the study illustrates the influence of memory on immune dynamics.