Votes to approve Thomas E. Perez as Labor secretary and Gina McCarthy as administrator of the Environmental Protection Agency quickly followed a deal to end a showdown over executive branch nominations.
The 59-40 vote on McCarthy came 133 days after the Senate received her nomination, the longest delay of any Cabinet-level nomination this year. Perez was confirmed 54 to 46, to become possibly the first Cabinet secretary to win no votes from the opposition party, according to the Senate Historical Office.
It's unclear whether Perez would have been confirmed if not for the accord reached Tuesday in which Republicans agreed to allow votes on some presidential nominees.
Republicans had mounted fierce opposition to his nomination, focusing on his work at the Justice Department to orchestrate a deal in which St. Paul, Minn., agreed to drop a case pending before the Supreme Court that the administration believed could undermine enforcement of laws against housing discrimination. In return, federal officials agreed not to support a whistle-blower's lawsuit against the city.
That amounted to "an extraordinary amount of wheeling and dealing" outside Perez's responsibilities as assistant attorney general for civil rights, Sen. Lamar Alexander of Tennessee, the top Republican on the Health, Education, Labor and Pensions Committee, said before Thursday's vote.
Perez will become the only Latino in the Cabinet, leading the Labor Department as Congress considers a major overhaul of immigration laws that could create millions of newly legal workers.
Obama announced Perez in March as his choice to replace former California congresswoman Hilda L. Solis, who stepped down after four years to prepare for a possible campaign for the Los Angeles County Board of Supervisors.
The president has named 11 candidates for Cabinet-level positions in the first four months of his new term. All have now been confirmed. He will have another slot to fill when Janet Napolitano, secretary of the Department of Homeland Security, departs in September to head the University of California system.
The deal on executive nominations also led to the confirmation of Richard Cordray to lead the Consumer Financial Protection Bureau after a more than two-year delay and Fred Hochberg to continue as president of the Export-Import Bank.
Next week, the Senate will consider a full slate of five nominees for the National Labor Relations Board, which could fill out the panel for the first time in nearly a decade.
In a statement, Obama thanked senators for confirming nominees "who have waited far too long for the yes-or-no votes they deserve." Perez and McCarthy met with the president in the Oval Office after the votes.
Also Thursday, the Senate Judiciary Committee unanimously advanced James B. Comey's nomination to be director of the FBI. A vote on Samantha Power, announced in June as nominee for U.S. ambassador to the United Nations, could come before the Senate adjourns for its August recess.