The cause was complications from chronic inflammatory demyelinating polyneuropathy, a neurological disorder, according to a statement from the Lugar Center, a Washington nonprofit organization focused on weapons proliferation, food security and other issues that the Indiana Republican worked on in Congress.

Mr. Lugar began his public service career on the Indianapolis school board and drew national attention as the city’s mayor before winning election to the Senate in 1977. He twice chaired the Foreign Relations Committee — from 1985 to 1987 and from 2003 to 2007 — and he was the panel’s ranking Republican from 2007 until his defeat, by which time he was the longest-serving senator in Indiana history.

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The cerebral, soft-spoken former Eagle Scout and Rhodes scholar never claimed to be a colorful personality. “Dick has maintained that childhood capability of walking into an empty room and blending right in,” former Environmental Protection Agency administrator William Ruckelshaus, a fellow Hoosier and a friend, once joked at a Lugar roast.

But Mr. Lugar’s civility and grasp of substantive issues drew widespread respect. “He was kind of the E.F. Hutton of the Senate. When he spoke, people listened, because they knew that he had independently thought through his position and weighed it on the merits,” Michael J. Glennon, an international law professor at Tufts University and former legal counsel to the Senate committee, said in an interview, referring to well-known brokerage commercials from the 1970s and ’80s.

After Mr. Lugar’s defeat, John F. Kerry (D-Mass.), then chairman of the Foreign Relations Committee, called the loss “a tragedy for the Senate. . . . His expertise on complicated issues honed over 36 years simply can’t be replicated.”

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Mr. Lugar ran for president in 1996, vowing to test whether voters valued “serious talk about issues” over “cheap shots and sound bites.” The answer was not encouraging. Neither his sober — some said wooden — campaign appearances nor his proposal for a national sales tax attracted much interest. He seemed “like a fox-trot man caught in a rock-and-roll culture,” New York Times reporter R.W. Apple Jr. observed at the time.

“I think the momentum is suspect and the money is gone,” Mr. Lugar quipped as he bowed out after low-digit finishes in the early primaries.

His hopes for the vice presidency also went unfulfilled. In 1980, he was on Ronald Reagan’s shortlist but didn’t get the nod, and in 1980, George H.W. Bush tapped Indiana’s junior senator, Dan Quayle, as his running mate. Mr. Lugar never complained publicly.

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A moderate conservative who came of age during the Cold War, he viewed the proliferation of weapons of mass destruction as the most serious threat to national security, and it was in that area that he left his greatest mark.

As the Soviet Union collapsed, he and other policymakers feared its nuclear, chemical and biological weapons might fall into the wrong hands. In 1991, Mr. Lugar teamed with the Senate Armed Services Committee chairman, Sam Nunn (D-Ga.), to push through legislation to help Russia and other former Soviet republics secure their arsenals and, in most cases, dismantle them entirely.

The initiative — officially the Cooperative Threat Reduction Program but better known as Nunn-Lugar — provided funding and expertise that during the next two decades led to the deactivation of more than 7,500 nuclear warheads and hundreds of other weapons and delivery systems, according to the Defense Department. Ukraine, Belarus and Kazakhstan eliminated all of their nuclear arms.

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After Nunn retired in 1997, Mr. Lugar continued to promote the program and its expansion to countries outside the old Soviet empire.

“His legacy . . . is the thousands of missiles and bombers and submarines and warheads that no longer threaten us because of his extraordinary work,” President Barack Obama said in 2013 as he awarded Mr. Lugar the Presidential Medal of Freedom, the nation’s highest civilian honor.

Mr. Lugar was also a key supporter of arms-control treaties, including a pact banning chemical weapons that was ratified in 1997 over conservative GOP opposition. In 2010, he worked closely with the Obama administration to overcome similar resistance to the New START nuclear-weapons-reduction treaty with Russia.

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In his first stint as chairman of the Foreign Relations Committee, Mr. Lugar played an influential role on two hot-button issues. Although a faithful supporter of Reagan’s agenda, he led the Senate in overriding Reagan’s veto of legislation imposing stiff economic sanctions on apartheid South Africa. He also helped bring about the ouster of Marcos in the Philippines.

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As leader of a congressional delegation, Mr. Lugar traveled to the Philippines to observe the 1986 presidential election and told Reagan that widespread vote fraud invalidated Marcos’s claim to reelection. Reagan, a friend of Marcos’s, initially stood by him, insisting that fraud had also been committed by the challenger, Corazon Aquino.

Mr. Lugar, however, refused to back down, telling PBS’s “MacNeil/Lehrer NewsHour” that Marcos should either hold new elections or leave office. Mr. Lugar was not alone in urging a tough stand with Marcos, whose opulent lifestyle coupled with the country’s sliding economy was encouraging a Communist insurgency. But coming from a Reagan loyalist, Mr. Lugar’s comments added significant weight to the anti-Marcos push.

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In the end, Reagan withdrew his support, forcing Marcos to step down and securing the presidency for Aquino. Paying tribute to Mr. Lugar when he visited the Philippines in 1989, Aquino said his intervention had saved the U.S.-Philippine relationship, the Associated Press reported.

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Although Mr. Lugar was praised for his candor and diligence on the Philippine matter, he could frustrate colleagues yearning for a more consistently confrontational approach, according to journalist John T. Shaw’s book “Richard G. Lugar, Statesman of the Senate” (2012).

Mr. Lugar had concerns about the Bush administration’s plans to invade Iraq in 2003 and particularly its strategy for governing Iraq after Saddam Hussein’s removal from power in Baghdad. Yet Mr. Lugar voted to give the president broad authority to make war and did not forcefully criticize the administration’s Iraq policy until 2007.

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“I went to him a number of times and urged him to get more out front on Iraq,” former Republican senator Chuck Hagel, who was later a secretary of defense under Obama, told Shaw. “Dick opted to do it his way — quiet, private. I told him the White House wasn’t going to listen to him that way.”

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As chairman of the Agriculture Committee from 1995 to 2001, Mr. Lugar pushed to reduce crop subsidies, a position unusual for a legislator from a farm state and unwelcomed by farming interests. As the manager of his family’s 604-acre farm outside Indianapolis, he had hands-on knowledge of federal crop programs and considered them largely wasteful.

Mr. Lugar was such an institution that when he ran for a sixth term in 2006, the Democrats did not put up an opponent. But by 2012, the tea party revolution was in full swing, and an old complaint — that Mr. Lugar was more concerned with the world’s problems than Indiana’s — had gained resonance.

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“I think it’s fair to say that he has visited the Russian Federation more often than Russiaville, Ind.,” said the campaign manager for Mr. Lugar’s Republican challenger, then-state Treasurer Richard Mourdock. Disclosure that the 80-year-old incumbent had sold his Indianapolis home more than three decades earlier but still used it as his voting address reinforced the out-of-touch claim.

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Portraying Mr. Lugar as too liberal, Mourdock hammered at his votes for financial bailout legislation and Obama’s two Supreme Court nominees. Mourdock won the primary with 60 percent of the vote but in November lost to Joe Donnelly, a Democrat.

Gathering laurels

Richard Green Lugar was born in Indianapolis on April 4, 1932. His solidly Republican family owned a company that manufactured biscuit-making equipment and had a farm, which Mr. Lugar continued to oversee while in the Senate.

The Lugar household was full of books and academic expectations. Richard made much use of the former and satisfied the latter. He was high school valedictorian, and in 1954, he graduated, first in his class, from Denison University in Ohio.

In 1956, he married his class co-president, Charlene Smeltzer. In addition to his wife, survivors include their four sons, Mark, Robert, John and David; a sister; 13 grandchildren; and 17 great-grandchildren.

After his two years as a Rhodes scholar at the University of Oxford in England, Mr. Lugar joined the Navy, completed Officer Candidate School and was assigned to the Pentagon as intelligence briefer for Adm. Arleigh Burke, chief of naval operations.

Mr. Lugar returned to Indianapolis in 1960 and helped his brother Tom manage the family company. He also won a seat on the local school board, where his reform efforts were noticed. In 1967, at 35, he ran for mayor, pledging to revitalize the city, and was elected to the first of two terms.

His initiatives — including the merger of city and county agencies — were praised by President Richard M. Nixon, and Mr. Lugar was proclaimed “Richard Nixon’s favorite mayor.” The title was bestowed by a reporter, not Nixon, but it nevertheless brought him national prominence.

In 1974, Mr. Lugar ran for the U.S. Senate against a popular Democratic incumbent, Birch Bayh. He lost, but two years later he easily defeated the state’s other Democratic incumbent, Vance Hartke, and thereafter, he had little trouble dispatching Democratic challengers.

After leaving the Senate, he created the Lugar Center. Among other projects, the center joined with Georgetown University to produce the Bipartisan Index — a ranking of members of Congress by how often they co-sponsor legislation with members of the other party.

The index echoed a message in Mr. Lugar’s Senate farewell speech. “Too often,” he told his colleagues, “we have failed to listen to one another and question whether the orthodox views being promulgated by our parties make strategic sense for America’s future.”

Brown is a freelance writer.