Moniz, 68, a professor at the Massachusetts Institute of Technology, replaces Steven Chu, who served as Energy secretary in President Barack Obama's first term. Moniz served as an energy undersecretary in the Clinton administration.
Sen. Ron Wyden, D-Ore., chairman of the Senate Energy Committee, called Moniz "solution-oriented" and said he is "smart about energy policy and savvy about Energy Department operations."
The 97-0 vote for Moniz came as Senate committees endorsed two other Cabinet nominees along party lines. The Senate Health, Education, Labor and Pensions Committee voted 12-10 to confirm Justice Department official Thomas Perez as labor secretary, and the Senate Environment and Public Works Committee voted 10-8 to advance assistant administrator Gina McCarthy to take over the Environmental Protection Agency.
Meanwhile, Senate Republicans said Thursday they would not support five Obama nominees to the National Labor Relations Board, raising the possibility that the troubled agency could be rendered mostly inoperable later this year.
The Senate vote on Moniz was delayed for more than three weeks after Sen. Lindsey Graham, R-S.C., objected to Obama's plan to cut about $200 million from a home-state project to turn weapons-grade plutonium into nuclear fuel. Graham and other Republicans said the president's budget proposal jeopardized a plant being built at South Carolina's Savannah River nuclear site.
Graham made clear Thursday he had nothing against Moniz, calling him a "fine fellow." Graham said he has other "leverage points" to continue putting pressure on the Obama administration to fully fund the Savannah River project.
Sen. Thomas Carper., D-Del., called Moniz "smart as a whip," with a knack for explaining things "so even I understand."
As energy secretary, Moniz will face an array of challenges, as the administration continues to promote renewable sources of energy such as wind and solar power, even as it pushed to promote traditional fuel such as oil and natural gas.
In particular, Moniz will soon decide whether to approve a major expansion of U.S. natural gas exports that could create thousands of jobs, spur economic growth and help offset the nation's enormous trade deficit.
Increased exports also could lead to further increases in hydraulic fracturing, a drilling technique also known as fracking that has allowed companies to gain access to huge stores of natural gas but raised widespread concerns about alleged groundwater contamination and even earthquakes.
Federal law requires the Energy Department to determine that natural gas exports are in the public interest before granting permits to countries that do not have free-trade agreements with the United States.
Moniz, who heads an energy initiative at MIT, is widely seen as sympathetic to the natural gas industry. At a Senate hearing last month, he called the "stunning increase" in natural gas production a "revolution" that has led to reduced emissions of carbon dioxide and other gases that cause global warming.
A recent study commissioned by the department concluded that exporting natural gas would benefit the U.S. economy even if it leads to higher domestic prices for the fuel.
Skip Horvath, president and CEO of the Natural Gas Supply Association, an industry group, called Moniz "informed, engaged and forthcoming" in his approach to natural gas. "His vast experience in energy will be an asset to the administration," Horvath said.