Abstract Background: Antibiotic-induced dysbiosis is associated with an increased risk of depression and anxiety in the general population. A diagnosis of cancer is associated with an immediately and dramatically elevated risk of psychiatric disorders, but the potential influence of prediagnostic antibiotic-induced dysbiosis is unknown. Methods: Based on a national cohort of cancer patients in Sweden, we included 309,419 patients who were diagnosed with a first primary malignancy between July 2006 and December 2013. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of first-onset psychosis, depression, anxiety, or stress-related disorders during the first year after cancer diagnosis for antibiotic use during the year before cancer diagnosis. Results: Compared with no antibiotic use, use of antibiotics was associated with a higher rate of the aforementioned psychiatric disorders (HR, 1.23; 95% CI, 1.16–1.30) after adjustment for sociodemographic factors, comorbidity, potential indications for antibiotics, and cancer stage and type. The magnitude of the association was higher for broad-spectrum antibiotics (HR, 1.27; 95% CI, 1.18–1.37), higher doses (HR, 1.32; 95% CI, 1.22–1.44), more frequent use (HR, 1.33; 95% CI, 1.21–1.46), and recent use (HR, 1.26; 95% CI, 1.17–1.35). Conclusions: Use of antibiotics, especially of broad-spectrum type, of high dose and frequency, with recent use, was associated with an aggravated risk of psychiatric disorders, compared with no antibiotic use. Impact: A better understanding of the microbiota–gut–brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.