Working in primitive conditions, Chagas described in detail a previously-unknown infectious disease, its pathogen, vector (Triatominae), host, clinical manifestations, and epidemiology.

[3] For his dissertation, his mentor, Francisco Fajardo, suggested that he work on malaria,[2] as the process of its transmission had been discovered by a British medical officer Ronald Ross in India in 1898.

His published work on this method served as the basis of prevention of malaria all over the world, and was adopted by a service of the Ministry of Health in Brazil, which was established expressly for this purpose.

In 1906, Chagas returned to Rio de Janeiro and joined the Oswaldo Cruz Institute, where he worked for the rest of his life.

[3] In 1907, there was an outbreak of malaria at the Minas Gerais hinterland, largely affecting railroad workers and greatly hampered the construction on new railway from Rio de Janeiro to the city of Belém in the Amazon.

Once we heard of the blood-sucking habits of this insect and of its proliferation in human dwelling-places, we became very interested in knowing its exact biology and above all in ascertaining if by any chance it were, as I immediately supposed, a transmitter of any parasite of man or of another vertebrate.

[8][3]He discovered that the intestines of these insects harbored flagellate protozoans, a new species of the genus Trypanosoma, and was able to prove experimentally that it could be transmitted to marmoset monkeys that were bitten by the infected bug.

He also persuaded Argentine physician Salvador Mazza to research the epidemic, leading to the latter's confirmation of the existence of Trypanosoma cruzi in Argentina in 1927, and eventually to government action.

[13] In 1909, he reported in the Brazilian medical journal, Brazil Médico, a case of human trypanosomiasis and noted the association with severe heart disease.

[14][15] In 1910, he further noticed that the parasitic infection could be classified into at least three different conditions, chronic heart disease, brain disorder, and thyroid problem, especially of goiter.

At the medical school, he was nicknamed "two-candle student" as he would use up two candles every evening for reading as there was no electricity in Rio de Janeiro at the time.

[2] One of his sons, Carlos Chagas Filho (1910–2000), became an eminent and internationally recognized scientist in the field of neurophysiology and president of the Pontifical Academy of Sciences.

Another son, Evandro Chagas (1905–1940), was also a physician and researcher in tropical medicine, who died in a plane crash at 35 years of age.

A hundred years after the discovery of the disease, speculation still remains regarding the two official nominations of Carlos Chagas for the Nobel Prize.

Analysis of the database of the Nobel Prize archives, with the revelation of the names of nominators, nominees, and prizewinners from 1901 to 1951, brought information not only about what was considered to be a scientific achievement at that time, but also about who the important scientists were and the relationships between them.

The connections of the members of the Nobel Committee with the international scientific community, almost exclusively centered in European and North American scientists, also influenced their choices.

The nonrecognition of Carlos Chagas' discoveries by the Nobel Committee appears to be more correctly explained by these factors than by the negative impact of the local opposition.