For Dr Biden, who has four university degrees, always vowed to continue her work as a community college professor even if her husband became the world’s most powerful politician.
And Dr Biden, who has five grandchildren, will be the first first lady to to have a full-time career outside of the White House.
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“If we get to the White House, I’m gonna continue to teach,” she told CBS News in November.
“It’s important, and I want people to value teachers and know their contributions, and lift up the profession.”
It will not be new territory for her though.
After Mr Biden was sworn in as Barack Obama’s vice president in January 2009, Dr Biden continued to teach at Northern Virginia Community College, with her secret service detail dressing like students to blend in.
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She was so successful that some students reportedly did not even know who “Dr B” was, and she even defended her dissertation using her maiden name of Jacobs.
“Most nights we had receptions so I would come home from school and I would take a half an hour down, and sometimes I would just be flat on my back on the bed getting my head together,” she told Vogue of being married to the vice president.
“And then I’d get up and go downstairs and do a receiving line.”
Dr Biden, 69, married her first husband, Bill Stevenson, at just 18 but their marriage only lasted five years.
In March 1975 she and Mr Biden went on their first date in her hometown of Philadelphia, Pennsylvania.
Mr Biden was a newly elected US senator for Delaware whose wife Neilia and infant daughter Naomi had been killed in a car accident in 1972.
““It was kind of a blind date that we went out on and I didn’t think I’d really — I thought, ‘OK, I’ll go out with him once and that’ll be it,’ ” she told the Philadelphia Inquirer.
“I just didn’t think he would appeal to me.”
But she told Vogue that after she got home from the date, where they saw A Man and a Woman at a cinema in Philadelphia she called her mother.
"When we came home he shook my hand good night,” she recalled.
“I went upstairs and called my mother at 1AM and said, 'Mom, I finally met a gentleman.'"
Mr Biden often uses the story on the campaign trail and says it took him two years and five proposals to convince his wife to marry him, and to become a stepmother to his two sons, Hunter and Beau.
In a video at the Democratic National Convention this summer, Mr Biden spoke about what his marriage had meant for their family.
“She put us back together. She gave me back my life. She gave us back a family,” he said.
Observers say Dr Biden is a big fan of playing pranks, and she once hid in an overhead bin on Air Force Two to surprise Mr Biden.
Dr Biden credits her parent’s relationship for that part of her character.
“Their marriage was strong and loving and full of laughter,” she told the Inquirer.
Delaware Senator, Chris Coons, a leading supporter of Mr Biden, has spoken glowingly of Dr Biden.
“Jill is someone who has a big heart. She’s a tough Philly girl, but she’s also gracious,” said Mr Coons told the Inquirer.
“To be blunt, one of the ways I gauge my colleagues is their spouses, and particularly with men I am closest to and most admire senators whose spouses are strong-willed, capable, independent people.”
The senator’s wife, Aimee Coons, told the Inquirer she was most impressed with Dr Biden’s independence from politics.
“You have to have your own identity. You have to believe in yourself first. Don’t give up yourself — be who you are,” said Ms Coons.
“She’s never been a political person. But she’s become such a strong and powerful voice for Joe and the campaign.”
Dr Biden has also been a forceful defender of her husband, both politically and physically.
In February she intervened when a heckler tried to confront Mr Biden at an event in New Hampshire, pushing the protestor away from him.
“I’m a good Philly girl,” she told reporters with a smile after the incident.
Then in March she jumped in to protect Mr Biden when two anti-dairy protestors separately charged towards him at a rally in Los Angeles, holding them off until they were removed by security.
Dr Biden says that if she became first lady she would focus on education and military families as her top priorities.
“The beauty of it is that you can define it however you want. And that’s what I did as Second Lady—I defined that role the way I wanted it to be,” she told Vogue.
“I would still work on all the same issues. Education would be right up there - and military families. I’d travel all over this country trying to get free community college.”
Dr Biden’s four sisters say she will be a “natural” first lady.
“She took care of me. She was there if I needed her,” said Bonny Jacobs.
“As she got older, I watched everything she did, she put on makeup and when she would leave I’d try her makeup on.
“The four of us are amazed, like, gee, our sister could be first lady.
“But, first lady is a natural transition for her.”