Significance The classical active penetration model for Toxoplasma invasion was established in studies of infection of nonphagocytic host cells by virulent strains of the parasite. Here, we show that avirulent Toxoplasma parasites use a noncanonical invasion pathway when infecting macrophages. Instead of active penetration at cell surface, avirulent Toxoplasma parasites are initially phagocytosed by macrophages and, subsequently, form a parasite vacuole from a phagosomal compartment. This phagosome to vacuole invasion (PTVI) pathway is associated with more efficient infection of macrophages. We hypothesize that PTVI represents a Trojan horse strategy for phagocyte infection and may lead to enhanced systemic dissemination and immune stimulation, acute infection control, and chronic infection establishment.