After the incubation period of 1 to 2 weeks, infected patients enter the acute phase of Chagas disease. Transfusion- and transplant-associated cases may have a longer incubation period, sometimes up to 120 days.

Patients in the acute phase have high levels of parasitemia detectable by light microscopy of peripheral blood.

Acute Chagas disease may be asymptomatic or can cause mild non-specific symptoms such as fever and lymphadenopathy, and usually passes undiagnosed. Rarely, T. cruzi infection results in acute myocarditis or meningoencephalitis with a high risk of mortality.