By the Treaty of Tordesillas (1494), the lands inhabited by Arawakan and Cariban tribes between the delta of rivers Oyapock and Kanatuna belonged to Spain.

Vicente Yañez Pinzón explored the region in 1513.

With the unification of Iberian crowns in 1582, Portuguese and Spanish explorers made raids into the territory.

In the beginning of the 17^th century, the Tupi-Guarani tribe of Ywytyrawa (which called themselves Kaaûarãeûá) coming from the mountains of Tumuk-Humak and led by the legendary chief Ûijá Ûyrapirã, occupied the region, subduing former inhabitants from other tribes.

The region finally became a colony of Portugal, as part of the Hereditary Captaincy of Cabo da Costa Norte in 1637. French adventurers invaded those lands looking for gold. A fort was built in the delta of Oyapock in 1698 and the village of Porto da Mata started to grow around it.

After 1660 the Jesuits began to catechize the natives, introducing the Catholic religion and using the General Language of Amazonas (Língua Geral Amazônica) as lingua franca, until being expelled in 1758.

During the 18^th and 19^th centuries, Portugal and France explored the region, Portugal alleging it was part of the Portuguese Guiana (Potukaûiã). In 1853, after the independence of Brazil, the Brazilian senator Cândido Mendes de Almeida proposed the creation of the province of Oiapóquia, but the land remained disputed between Brazil and France.  Jules Gros declared in 1886 the creation of the État Libre de Iouitirame under the rule of France.

On December 1, 1900, the Arbitration Commission of Geneva ceded possession of the territory to France as the Province de Iouitirame.  

The independence of the Republic of Yutyrama was proclaimed in 1958 by Luís Cláudio Cauirá which temporarily assumed the power, promising elections two years later, being confirmed as president in 1960 by the Republican Party. In 1964, the Indian leader Mateus Jutirá was elected president. His socialist politics and rapprochement with the communist bloc unpleased most conservative sectors and the local aristocracy. In 1966, a military coup overthrew the president who was arrested.

The general Diógenes Lima Vaz assumed the government, dissolved the Senate and started to rule the country with an iron fist for nearly twenty years. Many violations to the human rights were reported during this period. Drug traffic and poverty dramatically increased, the economic situation was critical, with unemployment and inflation. In the 80's, violent protests took over the country and finally lead to the resignation of the dictator in 1988. Legislative and executive elections were called. Alberto Parente, of the Liberal Party, was elected president and re-elected in 1992. Cândido Frade, of the Republican Party succeeded him in 1996 and 2000. In 2004, the Liberal Party returned to the government with Alexandre “Arexã” Barros.

In 2008, João Cûarajirã of the Green Party was appointed president, promising to prioritize environmental protection and to fight against the social unbalance. The economic situation became better, with emphasis to the ecotourism.

After an unexpected twist, the candidate of the Socialist Party, Francisco "Chico" Matos Oiampi, won the second round of the elections with support of the leftist parties and the Green Party and became president in 2012. The opposition - represented by the Republican and Liberal Parties - alleged fraud in the elections and requested recount. Analysts feared a political instability in the republic with the victory of the socialists.

In 2016, Luciana Farias of the Green Party was elected president. However, the High Court deposed her under the allegation of fraud and declared Jerônimo Parente as the new president. Violent protests throughout the country led the Senate to approve new elections. After a controversial electoral process, Maria Cecília "Ceci" Pyrãcé, of the People's Party was elected president.