Background: There is limited evidence in humans as to whether antibiotics impact the effectiveness of cancer treatments. Rodent studies have shown that disruption in gut microbiota due to antibiotics decreases cancer therapy effectiveness. We evaluated the associations between the antibiotic treatment of different time periods before cancer diagnoses and long-term mortality. Methods: Using the Clinical Practice Research Datalink GOLD, linked to the Cancer Registry’s and the Office for National Statistics’ mortality records, we delineated a study cohort that involved cancer patients who were prescribed antibiotics 0–3 months; 3–24 months; or more than 24 months before cancer diagnosis. Patients’ exposure to antibiotics was compared according to the recency of prescriptions and time-to-event (all-cause mortality) by applying Cox models. Results: 111,260 cancer patients from England were included in the analysis. Compared with antibiotic prescriptions that were issued in the past, patients who had been prescribed antibiotics shortly before cancer diagnosis presented an increased hazard ratio (HR) for mortality. For leukaemia, the HR in the Cancer Registry was 1.32 (95% CI 1.16–1.51), for lymphoma it was 1.22 (1.08–1.36), for melanoma it was 1.28 (1.10–1.49), and for myeloma it was 1.19 (1.04–1.36). Increased HRs were observed for cancer of the uterus, bladder, and breast and ovarian and colorectal cancer. Conclusions: Antibiotics that had been issued within the three months prior to cancer diagnosis may reduce the effectiveness of chemotherapy and immunotherapy. Judicious antibiotic prescribing is needed among cancer patients.