Information Minister Ernesto Villegas said Sabino Romero, a leader of the Yukpa tribe, was fatally shot on Sunday along a highway in the western state of Zulia.
Villegas said investigators suspect Romero may have been the victim of a hired killing, but authorities have not determined a motive.
"The investigation is under way," Villegas said. "We cannot put forth any type of hypothesis regarding this reprehensible act."
The Prosecutor General's Office issued a statement saying that Romero reportedly was gunned down by two assailants riding a motorcycle. The gunmen stopped a vehicle carrying Romero and sprayed it with bullets.
The indigenous leader's wife, Luisa Martinez de Romero, was wounded.
No suspects have been arrested.
Justice Minister Nestor Reverol told state television that federal police traveled from Caracas to Zulia to assist state authorities in investigating Romero's murder.
Reverol suggested that owners of large swaths of land located along the Perija mountain range may be responsible for Romero's murder.
Romero had "often denounced the complicity between local government authorities and landowners against the indigenous of the Perija area," David Smilde and Hugo Perez Hernaiz of the U.
In a message posted on Twitter, Zulia state Gov. Francisco Arias, a close ally of President Hugo Chavez, announced that federal and state officials would also join forces "to advance on the distribution of land for the Yukpas."
Romero had long campaigned for the rights of the Yukpa and the demarcation of their lands in the Perija mountain range bordering neighboring Colombia.
Foro por la Vida, a group of Venezuela's most prominent human rights organizations, issued a statement strongly condemning the killing, calling for an "exhaustive, transparent and quick investigation" to determine who was responsible.
Foro por la Vida noted that tensions between the Yukpa and cattle ranchers have increased in recent years, occasionally leading to violence, as the Indians have settled on lands claimed by ranchers and demanded the government initiate the demarcation of their ancestral lands.
Land owners are suspected of killing several tribe members amid land-related disputes, according to human rights organizations. Rights groups said the Yukpa repeatedly denounced threats from ranchers, but authorities failed to act.
"There's a lot of tension in the region," Lusbi Portillo, an Indian rights activist, told The Associated Press in an interview.
Portillo counts at least eight murders involving Yukpa tribe members in recent years.
"There are no investigations, nobody is arrested," added Portillo, a representative of Sociedad Homo et Natura, a non-governmental organization that closely tracks indigenous rights issues in Venezuela.
Portillo said that he has received anonymous death threats by telephone.
Following a fight between rival groups of Indians that ended with the death of one of those involved in the melee, Sabino Romero was arrested in 2009, charged with murder and put on trial, according to Esperanza Hermida, a representative of the local Provea human rights group.
Romero spent approximately 18 months in military custody as the trial continued. He was released in 2011 after prosecutors failed to produce evidence supporting their accusations.
"They used the fight to justify the accusations, which were aimed at stopping his protest activities," Hermida said in a telephone interview, referring to government officials.
Liliana Ortega of the Cofavic rights group said the government began "criminalizing" activists and organizations that spoke out against Romero's arrest and trial.
"A growing campaign of criminalization has been developing in Venezuela against social leaders, human rights activists and union leaders ... that take up critical positions against state policies," Ortega said.
Associated Press writers Fabiola Sanchez and Frank Bajak contributed to this report.
Christopher Toothaker on Twitter: http://twitter.com/ctoothaker