President Donald Trump's pick for EPA administrator was among the most contentious of his cabinet nominees, and Democrats held an all-night session on the Senate floor in a failed bid to block his confirmation.
Pruitt was confirmed largely along party lines, 52 to 46 - a clear relief for the White House two days after Trump's nominee for secretary of labor withdrew his nomination amid business and personal controversy.
Two Democrats from coal-rich states, Joe Manchin of West Virginia and Heidi Heitkamp of North Dakota, voted for Pruitt.
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As attorney general for the state of Oklahoma, the 48-year-old Republican has filed or joined in more than a dozen law suits to block key EPA rules, siding with industry executives and activists seeking to roll back various regulations on pollution, clean air and clean water.
He assumes control of an agency that under former president Barack Obama was responsible for implementing sweeping environmental regulations governing clean air and water, greenhouse gases and vehicle fuel emissions.
Pruitt's opponents scoffed at Trump's suggestion that Pruitt will be a capable environmental steward.
"Republicans are turning their backs on decades of bipartisan environmental progress," number two Senate Democrat Dick Durbin said.
"Pruitt has demonstrated time and again his unwillingness to accept the science of climate change and his contempt for the laws protecting our air and drinking water," he added.
During his confirmation hearing Pruitt countered critics who see him as a climate skeptic, telling senators that "human activity in some manner" affects climate change.
Democrats had called unsuccessfully for a delay on the vote until after Tuesday, the day a court has ordered the Oklahoma attorney general's office to release some 3000 emails between Pruitt or his team and executives of the fossil fuel industry.
