In cancer patients, appropriate diagnosis and management of infection are frequently challenging owing to subtle or atypical presentation. We investigated the effectiveness of infectious disease (ID) consultations and the Antimicrobial Stewardship Program (ASP) in a Japanese cancer center. This 36-month-period, single-institution, interrupted time series analysis was retrospectively conducted during April 1, 2018–March 31, 2021, to evaluate a two-phase intervention: Phase 1 (notification of antimicrobials by the infection control team) and Phase 2 (establishing an ID consultation service and implementing ASP). Among 32,202 patients hospitalized, 22,096 and 10,106 hospitalizations occurred at baseline and during intervention period, respectively. The Antimicrobial Stewardship Team (AST) provided feedback on specific broad-spectrum antimicrobials in 913 instances (347 appropriate [38%]; 566 inappropriate [62%]), and 440 ID consultations were completed, with a 75% overall acceptance rate for AST suggestions. In Phase 2, monthly carbapenem days of therapy (CAR-DOT) decreased significantly, and narrow-spectrum antibiotic usage increased significantly in both trend and level; monthly DOT of antipseudomonal agents decreased significantly in trend. The results of these analyses of antimicrobial use are consistent with the DOT-based data based on antimicrobial use density (AUD). The total number of inpatient specimens increased significantly; the trend of multidrug-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infections decreased, without changes in the incidence of other resistant organisms, all-cause in-hospital mortality, and length of stay. Actual and adjusted CAR purchase costs per patient-day decreased without significant changes in the actual and adjusted purchase cost per patient-day for all intravenous antimicrobials. Combining ID consultation and ASP reduced carbapenem use without negative patient outcomes. Their implementation could facilitate establishment of safe cancer treatment facilities in Japan and improve prognosis in cancer patients.