Context Fertility control offers a non-lethal management technique for iconic yet overabundant wildlife. Slow-release hormonal implants containing deslorelin show promise for managing free-ranging populations, particularly in peri-urban reserves, but most studies have been limited to captivity. Aims We investigated the efficacy and mechanism of deslorelin implants in free-ranging female eastern grey kangaroos (Macropus giganteus) under realistic management conditions. Methods We assigned females to a deslorelin (9.4 mg, n = 53) or placebo (n = 56) group at three peri-urban sites in Victoria, Australia, and monitored reproductive success for 3 years by observing young in the pouch. We tested the plasma LH response of control and treated females to exogenous GnRH, and compared the size of ovarian follicles between the two groups. Key results Deslorelin implants reduced fertility at all three sites. No deslorelin-treated females bred in Year 1 at Anglesea and Serendip versus 42% and 44% of control females respectively. At Plenty Gorge, 60% of deslorelin-treated females bred in Year 1 versus 100% of control females. In Year 2, between 11% and 39% of the treated females bred versus between 82% and 100% of control females at all sites. The contraceptive efficacy reduced by Year 3 when between 43% and 57% of the treated females bred versus between 85% and 100% of controls. A GnRH challenge elicited higher plasma LH concentrations in control than in treated females, and unlike untreated females, treated females lacked ovarian follicles >2 mm. Conclusions Deslorelin implants reduced fertility in free-ranging female eastern grey kangaroos over three successive breeding seasons. Chronic exposure to deslorelin desensitised the pituitary gland to GnRH and suppressed follicular development, but did not inhibit the development of a blastocyst, pregnancy or lactation in at least some females that had conceived before treatment. Implications Effective population management using deslorelin implants will require females to be re-treated on multiple occasions because the contraceptive effect lasts only a portion of their reproductive life. This would be practical only at sites where kangaroos are relatively easy to capture. The timing of treatment is also important in a species that undergoes embryonic diapause, particularly at sites providing high-quality habitat.