A former U.S. senator from Colorado, Salazar ran the Interior Department throughout President Barack Obama's first term and pushed renewable power such as solar and wind and the settlement of a longstanding dispute with American Indians.
With Environmental Protection Agency chief Lisa Jackson also leaving the administration and Energy Secretary Steven Chu expected to depart, Obama will have a clean slate of top officials overseeing energy and environment issues.
In a statement Wednesday, Obama said Salazar had helped "usher in a new era of conservation for our nation's land, water and wildlife" and had played a major role in efforts to expand responsible development of the nation's domestic energy resources.
Salazar said in a statement that the Interior Department was helping secure "a new energy frontier" and cited an aggressive agenda to reform oil and gas leases, which he said had increased offshore drilling safety.
Under his watch, the Interior Department has authorized nearly three dozen solar, wind and geothermal energy projects on public lands that provide enough electricity to power more than 3 million homes, Salazar said.
Obama has vowed to focus on efforts to bolster renewable energy in a second term while continuing to expand production of oil and natural gas. He also has made it clear he will focus on climate change, an issue he has acknowledged was sometimes overlooked during his first term.
Former Washington Gov. Chris Gregoire, a longtime Obama ally, is among those mentioned as a potential successor to Salazar, along with John Berry, director of the White House Office of Personnel Management. Berry is a former assistant interior secretary and the director of the National Zoo. Gregoire, whose term expired Wednesday, also is considered a candidate to head the Energy Department or the EPA.
Rep. Raul Grijalva, D-Ariz., a senior member of the House Natural Resources Committee and a favorite of the environmental community, also is believed to be under consideration for Salazar's position.
Salazar, 57, entered the Senate with Obama in 2005. At Interior, he gained the most attention for his role in the drilling moratorium, a key part of the administration's response to the April 2010 explosion of the Deepwater Horizon rig in the Gulf of Mexico that killed 11 workers. The resulting oil spill was one of the largest environmental disasters in U.S. history and led to the unprecedented shutdown of offshore drilling.
Business groups and Gulf Coast political leaders said the shutdown crippled the oil and gas industry and cost thousands of jobs, even aboard rigs not operated by BP PLC. But Salazar said the industry-wide moratorium was the correct call and that his ultimate goal was to allow deep-water operations to resume safely.
"Today, drilling activity in the Gulf is surpassing levels seen before the spill, and our nation is on a promising path to energy independence," Salazar said in his statement Wednesday.
The moratorium was lifted in October 2010, although offshore drilling operations did not begin for several more months. Some Gulf Coast lawmakers continue to complain about the slow pace of drilling permits under the Interior Department, which renamed and revamped the agency that oversees offshore drilling in the wake of the spill.
Salazar also approved the nation's first offshore wind farm, Cape Wind, off the Massachusetts coast.
On land, Salazar has promoted solar power in the West and Southwest, approving an unprecedented number of projects, even as oil and gas projects continued to be approved on federal land.
Salazar also oversaw a $3.4 billion settlement resolving a dispute with Native American tribes that had lingered for more than a decade.
Salazar was the fourth Interior secretary to consider a 1996 lawsuit by Elouise Cobell accusing the government of mismanaging land trust royalties for more than a century. But Salazar was the one who finally settled the case, said Jacqueline Pata, executive director of the National Congress of American Indians.
Salazar and Obama "made it very clear that one of the presidential campaign promises they were going to resolve was the Cobell lawsuit, and Salazar made it happen," Pata said.
Throughout his tenure, Salazar tangled with oil companies. He criticized the George W. Bush administration for what he called a "headlong rush" to lease public lands, saying officials treated oil and gas executives as if they were "the kings of the world." Soon after taking office, Salazar suspended 60 of 77 leases in Utah that had been approved under Bush, setting a confrontational tone that would continue the next four years.
Jim Noe, an oil executive and head of a shallow-water drilling coalition, said Wednesday that Salazar's actions "hurt the industry, thousands of workers and the small businesses and communities that depend upon them. We hope that future leadership at the Interior Department will be able to take a more balanced approach to natural resource development."
Frances Beinecke, president of the Natural Resources Defense Council, an environmental group, said Salazar worked to strike a balance between responsible energy development and vital environmental protection.
Salazar set a sound foundation for solar and wind power on federal lands, while protecting areas where development does not make sense, Beinecke said.
Sierra Club executive director Michael Brune hailed Salazar for opening seven new national parks and 10 wildlife refuges while protecting Arctic areas from offshore drilling.
Salazar's leadership "has helped put our nation on a path where protecting our natural legacy and wild lands is a priority, not an afterthought," Brune said.
Salazar is the second of Obama's two Hispanic Cabinet members to depart. Labor Secretary Hilda Solis said last week she is leaving.
Associated Press writers Julie Pace and Ken Thomas contributed to this report.
Follow Matthew Daly on Twitter: https://twitter.com/MatthewDalyWDC