Abstract Background Multimorbidity is a growing challenge worldwide. In this nationwide study, we investigated the prevalence of multimorbidity and polypharmacy at the time of diagnosis across 20 cancers. Methods We conducted a nationwide register-based cohort study of all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015. Multimorbidity was defined as one or more of 20 conditions (131 specific diagnoses) registered in the Danish National Patient Registry < 5 years before the cancer diagnosis. Polypharmacy was defined as five or more medications registered in the Danish National Prescription Registry and redeemed twice 2–12 months before the cancer diagnosis. Results We included 261,745 patients with a first primary cancer, of whom 55% had at least one comorbid condition at diagnosis and 27% had two or more. The most prevalent conditions at the time of cancer diagnosis were cardiovascular disease, chronic obstructive pulmonary disease, diabetes, stroke and depression/anxiety disorder. Polypharmacy was present in one-third of the cancer patients with antihypertensives, anti-thrombotic agents, anti-hyperlipidaemic agents, analgesics and diuretics as the most prevalent redeemed medications. Conclusion Among patients with a newly established cancer diagnosis, 55% had at least one comorbid condition and 32% were exposed to polypharmacy.