After voting to end debate, the Senate voted 59-40 to confirm Gina McCarthy as administrator of the Environmental Protection Agency, The Hill reported.
Earlier, the chamber confirmed Thomas Perez to lead the Labor Department in a 54-46 party-line vote.
Republican Sens. Lamar Alexander and Bob Corker, both of Tennessee; Susan Collins of Maine; John McCain and Jeff Flake, both of Arizona and Kelly Ayotte of New Hampshire voted to confirm McCarthy. Sen. Joe Manchin, D-W.Va., joined most Republicans in voting "nay."
"My fight is not with her, it's with the agency and the president," Manchin said ahead of the vote. "And the fight will continue until the EPA stops its over-regulatory rampage."
"I welcome today's confirmation of Tom Perez to serve as secretary of Labor," Obama said in a statement. "At the Department of Labor, Tom will help us continue to grow our economy, help businesses create jobs, make sure workers have the skills those jobs require, and ensure safe workplaces and economic opportunity for all."
The votes followed an agreement between Senate Democrats and Republicans this week to allow up-or-down votes on several executive department nominees.
Also Thursday, the Senate Judiciary Committee voted 18-0 to advance the nomination of James Comey as FBI director to the full Senate, The Hill reported.
The Senate Wednesday confirmed the nomination of Richard Cordray to lead the Consumer Financial Protection Bureau and Fred Hochberg to head the U.S. Export-Import Bank.