Significance Endometriosis is a chronic, incurable inflammatory disorder impacting 190 million women worldwide. Immune cells called macrophages are implicated in promoting endometriosis. Macrophages have different origins and their origin can dictate function. In this study we demonstrate that endometriotic lesion-resident macrophages are derived from the uterine lining (endometrium), the abdominal (peritoneal) cavity, and recruited bone-marrow precursors (monocytes). Endometriosis triggers continuous recruitment of monocytes that differentiate into macrophages that differ from those usually present within the peritoneal cavity. By depleting different populations, we demonstrate that endometrial macrophages are “proendometriosis” while monocyte-derived peritoneal macrophages are “antiendometriosis” acting to protect the cavity from lesion establishment. In the future, immune-based therapies may allow targeting of prodisease macrophages and/or harnessing of antiendometriosis macrophages in endometriosis.