Background: Atopic dermatitis (AD) is a chronic eczematous disorder characterized by intense itchiness. Systemic therapies for AD include Janus kinase (JAK) inhibitors and various biological agents. The effects of transitioning from the JAK1 inhibitor, upadacitinib, to the anti-interleukin 13 antibody, tralokinumab, remain unclear. Objective: This study evaluated the transition from 15 mg of upadacitinib to tralokinumab in patients with moderate-to-severe AD. Methods: This analysis included 20 patients who switched from 15 mg of upadacitinib to tralokinumab due to an inadequate response or adverse events (AEs). We assessed the total and regional eczema area and severity index (EASI), which included assessments of the head and neck, trunk, and upper and lower limbs, along with erythema, edema/papulation, excoriation, lichenification, and the peak pruritus numerical-rating scale (PP-NRS), initially (start of 15 mg of upadacitinib), at the transition point (week 0), and during follow-up at weeks 4 and 12. Results: The EASI, EASI of the four anatomical regions, and EASI of the four clinical manifestations significantly declined from baseline at weeks 4 and 12, with no substantial reductions from week 0. The PP-NRS score notably decreased from baseline at week 4. Achieving EASI of 50 and 75 improved post-switching. Conclusion Transitioning to tralokinumab substantially alleviated rash in patients with AD who experienced suboptimal responses or AEs to 15 mg of upadacitinib.