The Senate confirmed Lighthizer by a vote of 82 to 14 yesterday, with broad bipartisan support.
The 69-year-old is returning to familiar territory, having served as deputy US trade representative in the 1980s under president Ronald Reagan.
Much of Trump's trade agenda has been on hold since Lighthizer's nomination in January.
He will now be thrust into tense trade talks, as Trump seeks to renegotiate the longstanding North American Free Trade Agreement (NAFTA) with Canada and Mexico and mulls potential tariffs and other import programs.
Trump, following through on an "America first" campaign pledge, abandoned the 12-nation Trans-Pacific Partnership in January.
In a statement following his January nomination Lighthizer said he was "fully committed to President-elect Trump's mission to level the playing field for American workers."
As deputy USTR in the 1980s, he declared his opposition to unfettered free trade, arguing for more "pragmatism" in trade policy.
He succeeds Michael Froman, who held the position under Democratic president Barack Obama.
Yesterday's confirmation finalizes Trump's cabinet-level appointments nearly four months after he entered the White House.
The position of USTR was created in 1962, and holds cabinet-level rank. In addition to negotiating trade deals, the USTR represents Washington in the World Trade Organization (WTO) and publishes annual reports on US trade policy.
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