Pruritus, skin pain, and sleep disturbance are a significant burden to individuals with moderate-to-severe atopic dermatitis (AD) and negatively impact quality of life. Fit-for-purpose patient-reported outcome measures (PROMs) that assess AD-related pruritus, skin pain, and sleep disturbance are important for evaluating the effectiveness of new AD treatments. To evaluate content validity of five AD-related PROMs in adolescents and adults with moderate-to-severe AD (the Worst Pruritus Numeric Rating Scale [NRS], the AD Skin Pain NRS; the Sleep Disturbance NRS, the skin pain-specific Patient Global Impression of Change [PGIC], and the skin pain-specific Patient Global Impression of Severity [PGIS]) and to assess patient-reported experience with pruritus, skin pain, and sleep disturbance. A qualitative study in adolescents (aged 12-17 years) and adults with moderate-to-severe AD was conducted in two consecutive stages. In each stage, two iterative rounds of individual interviews were conducted by experienced interviewers. All interviews included concept elicitation and cognitive debriefing components. Data were analysed using thematic analysis. A total of 27 adults and 20 adolescents with moderate-to-severe AD participated in the initial content evaluation (Stage 1) of the Worst Pruritus NRS [1.0] and AD Skin Pain NRS [1.0] (n = 26; 16 adults, 10 adolescents) and in the subsequent content evaluation (Stage 2) of the revised Worst Pruritus NRS [1.1], revised AD Skin Pain NRS [1.1], Sleep Disturbance NRS, skin pain-specific PGIC, and skin pain-specific PGIS (n = 21; 11 adults, 10 adolescents). Results were generally aligned and consistent for both adult and adolescent participants. Additionally, we found that sleep disturbance is relevant and important for evaluation in adults and adolescents with moderate-to-severe AD (Stage 2), while also providing further confirmation of this for pruritus and skin pain (Stages 1 and 2). Our findings support the content validity of the revised Worst Pruritus NRS [1.1], revised AD Skin Pain NRS [1.1], Sleep Disturbance NRS, skin pain-specific PGIC, and skin pain-specific PGIS in individuals aged ≥12 years with moderate-to-severe AD. Furthermore, the findings support sleep disturbance, skin pain, and pruritus as being relevant and important features for both adolescents and adults with moderate-to-severe AD.