Background Hypothyroidism is a commonly diagnosed endocrinopathy in dogs. This study aimed to investigate the frequency and risk factors for diagnosis of hypothyroidism in UK primary-care practice. Dogs diagnosed with hypothyroidism were identified by searching electronic patient records of primary-care practices participating in VetCompass. A cohort study design estimated one-year (2016) period prevalence and incidence risk for hypothyroidism. Multivariable binary logistic regression models were used to evaluate associations between demographic risk factors and hypothyroidism. Results From 905,553 dogs, 2,105 dogs were recorded with diagnosed hypothyroidism in 2016; 359 incident and 1,746 pre-existing, giving an annual prevalence of 0.23% (95% CI 0.22–0.24) and annual incidence risk of 0.04% (95% CI 0.04–0.04). Multivariable logistic regression identified 24 predisposed and nine protected breeds. Standard Doberman pinscher (odds ratio [OR] = 17.02, 95% CI 12.8–22.64), Tibetan terrier (11.25, 95% CI 8.27–15.32) and boxer (10.44, 95% CI 8.66–12.58) breeds showed high predisposition. Pug (OR 0.29, 95% CI 0.09–0.89), Yorkshire terrier (OR 0.38, 95% CI 0.24–0.59), Shih-tzu (OR 0.38, 95% CI 0.23–0.64) and Jack Russell terrier (OR 0.40, 95% CI 0.29–0.54) were the most protected breeds. Overall, being a purebred dog, being insured, having bodyweight above the breed-sex mean, increasing age, being neutered and rising adult bodyweight also showed increased odds being a dog living with a diagnosis of hypothyroidism. Conclusions Several strong breed predispositions for diagnosis of hypothyroidism were identified that can assist with disorder prioritisation in ongoing efforts to improve breed health. Other risk factors were also identified that can assist veterinary surgeons during clinical work-up of suspected cases. Identification of novel evidence for protected breeds provides useful information for research into genetic mechanisms.