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Background: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult‐onset AD. We aimed to characterize factors associated with adult‐onset versus childhood‐onset AD and controls. Methods: We analyzed cross‐sectional data of the CK‐CARE‐ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood‐onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult‐onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non‐atopic)). Results: We identified active smoking to be associated with adult‐onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06–29.01] vs. controlsnon‐atopic, aOR = 4.03 [1.20–13.45] vs. controlsatopic). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14–0.91]). Food allergy (aOR = 2.93 [1.44–5.96]), maternal food allergy (aOR = 9.43 [1.10–80.95]), palmar hyperlinearity (aOR = 2.11 [1.05–4.25]), and academic background (aOR = 2.14 [1.00–4.54]) increased the odds of childhood‐onset AD versus controlsatopic. Shared AD‐associated factors were maternal AD (4‐34x), increased IgE (2‐20x), atopic stigmata (2‐3x) with varying effect sizes depending on AD onset and control group. Patients with adult‐compared to childhood‐onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12–4.13]), but reduced odds to feature multiple (3–4) atopic comorbidities (aOR = 0.34 [0.14–0.84]). Adult‐onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood‐onset AD, particularly infant‐onset, mainly in "high‐atopic"‐clusters. Conclusions: The identified associated factors suggest partly varying endo‐ and exogeneous mechanisms underlying adult‐onset versus childhood‐onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non‐smoking and physical activity as modifiable lifestyle factors. [ABSTRACT FROM AUTHOR]