Epidemiological data on depression and anxiety in Guatemala is lacking. Using 2016 National Disability Survey data, we explored the sociodemographics of people with anxiety and/or depression and its heightened burden on access to key services. The survey (n = 13,073) used the Washington Group Extended Set to estimate disability prevalence, including anxiety and/or depression. A nested case-control study was included to explore the impact of disability on key life areas. Cases (indicating 'A lot of difficulty' or 'Cannot do' in one or more functional domain) and age-/sex-matched controls were administered a structured questionnaire. Multivariable logistic regression and heightened-burden analysis were conducted. Higher odds of anxiety and/or depression were found in participants who were 50+ (aOR 2.3, 1.8-3.1), female (aOR 1.8, 1.4-2.2), urban (aOR 1.5, 1.2-1.9), divorced/separated (aOR 2.0, 1.3-3.0), and widowed (aOR 1.6, 1.0-2.4), as well as those with impaired communication or cognition (aOR 17.6, 13.0-23.8), self-care (aOR 13.2, 8.5-20.5), walking (aOR 13.3, 9.7-18.3), hearing (aOR 8.5, 5.6-13.1), and vision (aOR 8.5, 6.1-11.8). Lower odds of anxiety and/or depression were found in participants with a university education (aOR 0.2, 0.5-0.9), and those living in the southeast (aOR 0.2, 0.1-0.3) or northeast (aOR 0.3, 0.2-0.4). Compared to people with impairments that were not depression and/or anxiety, people with depression and/or anxiety were less likely to receive a retirement pension (aOR 0.4, 0.2-0.8), and more likely to receive medication for depression/anxiety (aOR 4.1, 1.9-9.1), report a serious health problem (aOR 1.8, 1.3-2.5), and seek advice/treatment with a government health worker/health post (aOR 6.3, 1.0-39.2).