The International Criminal Court (ICC) will investigate whether crimes against humanity were committed during Venezuela's crackdown on anti-government protests in 2017.
Venezuela's President Nicolas Maduro said the state respects the decision to investigate, but does not share it.
More than 100 people died during the clampdown on protesters.
The demonstrations started after the Supreme Court decided to dissolve the opposition-dominated National Assembly.
The ICC's Chief Prosecutor Karim Khan announced the move after a three-day trip to Caracas.
Both Venezuela's opposition and its government have urged the ICC to investigate alleged crimes carried out by their opponents.
Opposition leader Juan Guaidó, who claims to be Venezuela's interim president and has the backing of more than 50 countries, welcomed the development.
Writing on Twitter, he said it would enable the victims and their families to "claim the right to obtain justice that has been denied in Venezuela".
Human Rights Watch said the investigation "offers a pathway to justice for victims of atrocities" by Mr Maduro's government.
"The ICC's first investigation in the Americas comes on the back of the extreme repression the Maduro government has inflicted on the Venezuelan people," José Miguel Vivanco, Americas director at Human Rights Watch, said in a statement.
Mr Khan said his job was to uphold the rule of law, not to settle political scores.
"I ask everybody now, as we move forward to this new stage, to give my office the space to do its work," he said. "I will take a dim view of any efforts to politicise the independent work of my office."
Mr Maduro has complained that the government was not granted access to documents and information during the ICC's preliminary investigation in 2018.
"We were blind in that stage," the president said.
Some 150 police and military members have been charged or sentenced for human rights violations over Venezuela's 2017 crackdown, according to the public ministry.
The opposition says these prosecutions were simply an effort to avoid an ICC probe.
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