Background: Atopic dermatitis (or eczema) is a chronic inflammatory disorder associated with sleep disturbances and quality-of-life impairment. Sleep disturbances have been shown to cause headaches in childhood. However, an association between eczema and headaches is not well established. Objectives: We sought to determine whether childhood eczema is associated with increased headaches and whether such association is related to fatigue or sleep disturbance. Methods: We analyzed data from 401,002 children and adolescents in 19 US population-based cross-sectional studies from the National Survey of Children's Health 2003/2004 and 2007/2008 and the National Health Interview Survey 1997-2013. Results: In multivariate models controlling for age, sex, race/ethnicity, household income, highest level of education in the family, insurance coverage, number of persons in the household, birthplace in the United States, ever history of asthma, hay fever, and food allergy, eczema was found to be associated with headaches in 14 of 19 studies. In a pooled analysis of all 19 studies, children with eczema compared with those without eczema had a significantly higher prevalence (10.7% [95% CI, 10.3% to 11.0%] vs 5.4% [95% CI, 5.3% to 5.5%]) and odds (1.52 [95% CI, 1.45-1.59]) of headaches. Mild (1.79 [95% CI, 1.07-2.98]) and severe (2.72 [95% CI, 1.33-5.57]) eczema were associated with significantly higher odds of headaches. In particular, eczema associated with atopy, fatigue, excessive daytime sleepiness, insomnia, and only 0 to 3 nights of sufficient sleep had even higher odds of headache than eczema alone. Conclusions: Eczema is associated with increased headaches in childhood, particularly in patients with severe disease accompanied by atopy, fatigue, and sleep disturbances.