That bid collapsed when McCain and Republican Senator Lindsey Graham accused Rice of misleading Congress over what caused the terrorist killing of Ambassador to Libya Christopher Stevens and three Americans at the Benghazi consulate in September. This week Clinton agreed "systemic"security failures had occurred in Libya and four officials reportedly resigned.
Rice stood down last week. Suddenly, Kerry, who has hovered in the wings for weeks, was centre stage.
Clinton is a hard act to follow, respected by many foreign leaders. But Kerry has decades of foreign policy experience and a formidable list of top overseas contacts.
"I've been doing this all my life," Kerry told the Boston Globe in June.
And while Obama might have preferred someone from his own generation, such as Rice, Kerry, 69 - whose background includes a Swiss boarding school, Yale and marriage to heiress Teresa Heinz Kerry - is a seasoned negotiator, troubleshooting for US presidents since he was first elected to the Senate in 1984.
In 1994 the senator, who commanded patrol craft in the Mekong Delta, later heading an anti-war group and testifying before the SFRC, joined with McCain in ending a trade embargo against Vietnam, paving the way for full relations.
He has defused crises for Obama, persuading Afghan President Hamid Karzai to accept a run-off election in 2009 after a corrupt contest, and soothing Pakistani egos after the US killed Osama bin Laden there.
But Kerry's efforts to bring Syrian President Bashar al-Assad to heel - including suggesting Nato airstrikes, opposed by the President - failed.
Some suggest this divergence may be a plus, allowing both men to forge new ground. "There are very few people with greater experience over a longer period of time," Nicolas Burns, a former diplomat who has served US Administrations since Bill Clinton, told CNN. He said Kerry, who would be the first white man to serve as the top US diplomat since Warren Christopher in Clinton's second term, can "drill several layers deep on foreign policy issues".
And while Kerry is not part of the President's inner circle (nor was Clinton), he invited Obama to make the keynote speech at the 2004 Democratic National Convention rocketing the Illinois senator into the spotlight.
If Kerry gets the nod, he will have to hit the ground running. Besides the gruelling schedule of day-to-day crisis management, he must grapple with tectonic shifts in the global balance of power, where US hegemony is waning. The recent Global Trends 2030; Alternative Worlds report, issued by the US National Intelligence Council, forecasts America's economy will be eclipsed by China in the next two decades as Western power and wealth flows to Asia.
"China alone will probably have the largest economy, surpassing that of the US a few years before 2030," it says. "Meanwhile, the economies of Europe, Japan and Russia are likely to continue their slow relative decline."
Nonetheless, it suggests the US will remain a superpower, the only nation able to forge coalitions that can respond to international challenges.
"China isn't going to replace the US on a global level," said Mathew Burrows, the report's leading author. "It isn't necessarily the largest economic power that is going to be the superpower."
Maybe. But the on-going "pivot", as America's military assets and political resources are redirected into the Asia-Pacific region, suggests the US is hedging its bets.
Kerry's elevation to State could complement other national security cabinet changes. At press time Republican Senator Chuck Hagel was tipped to replace Leon Panetta as Defence Secretary. Rice may replace Thomas Donilon as National Security Adviser. And acting CIA director Michael Morell, who filled the slot vacated by disgraced General David Patraeus, may get the job permanently. It is a seasoned line-up that stresses pragmatism.
"There are so many urgent issues clamouring for attention that an issue that falls under the headline of important, but not urgent, will struggle to get attention," says Gayle Tzemach Lemmon, a Fellow with the Council of Foreign Relations.
As the Secretary must deal with fallout from the Arab Spring, the wind-down in Afghanistan - a huge task that is often overlooked - Iran's nuclear programme, the Syrian revolution, the Israeli-Palestinian impasse, and volatile relations with China and Russia, the only big issue Lemmon suggests could squeeze on to the US agenda will be the unsolved global economic crisis.
And restructuring at home is also likely. Lemmon says Americans are "feeling decidedly less ambitious in terms of what they want to do in the world" - although that potentially isolationist trend is not shared by the White House - and there is pressure to cut staff at the State Department.
John Forbes Kerry
Age: 69
Education: Bachelor's degree, political science, Yale University, 1966; law degree, Boston College, 1976.
Experience: US Senate, 1985-present; unsuccessful Democratic candidate for President, 2004; Massachusetts lieutenant governor, 1983-1985; lawyer in private practice, 1979-1982; Middlesex County, Massachusetts, prosecutor, 1976-1978; spokesman, Vietnam Veterans Against the War, 1971; Navy officer, awarded Silver Star, Bronze Star with Combat "V," three Purple Hearts for Vietnam War service, 1966-1970.
Family: Wife, Teresa Heinz; two children, three stepchildren, two grandchildren.
Quote: "I've known and worked closely with Susan Rice not just at the UN, but in my own campaign for President. I've defended her publicly and wouldn't hesitate to do so again because I know her character and I know her commitment. She's an extraordinarily capable and dedicated public servant."