For most of his 30 years as Pennsylvania's longest-serving U.S. senator, Specter was a Republican, though often at odds with the GOP leadership. His breaks with his party were hardly a surprise: He had begun his political career as a Democrat and ended it as one, too.
In between, he was at the heart of several major American political events. He drew the lasting ire of conservatives by helping end the Supreme Court hopes of former federal appeals Judge Robert H. Bork and the anger of women over his aggressive questioning of Anita Hill, a law professor who had accused Supreme Court nominee Clarence Thomas of sexual harassment. He even mounted a short-lived run for president in 1995 on a platform that warned his fellow Republicans of the "intolerant right."
Specter never had his name on a piece of landmark legislation. But he involved himself deeply in the affairs that mattered most to him, whether trying to advance Middle East peace talks or federal funding for embryonic stem cell research. He provided key votes for President Barack Obama's signature accomplishments, the health care and economic stimulus bills.
Specter died at his home in Philadelphia from complications of non-Hodgkin lymphoma, said his son Shanin. Over the years, Specter had fought two previous bouts with Hodgkin lymphoma, overcome a brain tumor and survived cardiac arrest following bypass surgery.
"For over three decades, I watched his political courage accomplish great feats and was awed by his physical courage to never give up. Arlen never walked away from his principles and was at his best when they were challenged," said Vice President Joe Biden, with whom Specter often rode the train home from Washington, D.C., when Biden also served in the Senate.
Said former Pennsylvania Gov. Ed Rendell, "Arlen wanted to die in the Senate, and in many ways he should have."
Intellectual and stubborn, "snarlin' Arlen" took the lead on a wide spectrum of issues and was no stranger to controversy.
He rose to prominence in the 1960s as an assistant district attorney in Philadelphia prosecuting Teamsters officials for conspiracy to misuse union dues and as counsel to the Warren Commission, where he developed the "single-bullet fact" in Kennedy's assassination, as he called it.
He came to the Senate in the Reagan landslide of 1980 and, as one of the Senate's sharpest legal minds, took part in 14 Supreme Court confirmation hearings.
Specter lost his job amid the very polarization that he had repeatedly attacked: He crossed political party lines to make the toughest vote he had ever cast in his career when, in 2009, he became one of three Republicans to vote for President Obama's economic stimulus bill.
Specter, who grew up in Depression-era Kansas as the child of Jewish immigrants, justified his vote as the only way to keep America from sliding into another depression.
But Republican fury over his vote appeared immovable and in one of his last major political acts, Specter startled fellow senators in April 2009 when he announced he was joining the Democrats at the urging of good friends Biden and Rendell, both Democrats.
Still, many Democratic primary voters had never voted for Specter, and they weren't about to start. Instead, they picked his primary opponent, then-U.S. Rep. Joe Sestak, despite Specter's endorsement from Obama, Rendell and Biden.
Born in Wichita, Kan., on Feb. 12, 1930, Specter spent summers toiling in his father's junkyard in Russell, Kan., where he knew another future senator — Bob Dole. The junkyard thrived during World War II, allowing Specter's father to send his four children to college.
Specter left Kansas for college, graduating from the University of Pennsylvania in 1951 and Yale law school in 1956. He served in the Air Force from 1951 to 1953. After working on the Warren Commission, he returned to Philadelphia and wanted to run for district attorney in 1965. But he found that he would have to challenge not only his boss, but the city's entrenched Democratic Party. Specter ran as a Republican and won.
Friends say his childhood circumstances made him determined, tough and independent-minded. In his 2000 book, "Passion for Truth," he noted how his father had complained bitterly that the U.S. government had broken its promise to pay a bonus to World War I veterans.
"Figuratively, "he wrote, "I have been on my way to Washington ever since to get my father's bonus."
For Specter, the benefit of crossing party lines wasn't always about being true to his convictions. He also used it to benefit the causes he championed.
"He was a master politician," Rendell said. "He was as smart as a whip."
In 2001, he voted for President George W. Bush's package of tax cuts, but voted with Democrats to route $450 billion into education and debt reduction. He negotiated $10 billion for medical research when he agreed to vote for the stimulus.
But Specter also believed in the political middle, and often lamented the disappearance of moderates who had the courage to buck party leadership.
In one study of congressional polarization, University of Georgia professor of political science Keith Poole mapped the political polarization of Congress by charting votes and found that the parties are more divided than at any time since Reconstruction after drifting further apart in the last 40 years.
Poole said in an essay that there are no true moderates left in the House of Representatives, and just a handful remaining in the Senate, in contrast to the Reagan era when about half of the members of Congress could be described as moderates.
The other two Republicans who supported Obama's stimulus are Maine's two U.S. senators. One of them, Olympia Snowe, announced in February that she wasn't seeking re-election. She said she was frustrated by "'my way or the highway' ideologies."
Specter's funeral was scheduled for Tuesday in Penn Valley, Pa., and will be open to the public, followed by burial in Huntingdon Valley, Pa.
Besides his son, Shanin, Specter is survived by his wife, Joan, son, Steve, and four granddaughters.