Duckworth said she was excited to get to Washington and get to work. "No matter who you voted for today, we're all in this together," she said.
Duckworth made note of her fellow soldiers who rescued her after the Army helicopter she was in crashed in Iraq in 2004, resulting in the loss of her legs. "I live every day trying to honor you," she said at a victory rally.
Earlier, Kirk said he had called Duckworth to concede the race and invited her to have a beer at the Billy Goat Tavern. "I told her I would do everything possible to help her," Kirk said.
Duckworth thanked Kirk, who was first elected to the U.S. House in 2000 and the Senate in 2010, saying he "has served the country for over two decades and we are grateful for his service."
Kirk, who suffered a stroke in 2012 and uses a wheelchair, has become an inspiration for other people dealing with disabilities, she said.
"I believe in an America that doesn't give up on anyone who hasn't given up on themselves," she said.
Duckworth had led in polls by a significant margin throughout the campaign.
With half of Chicago precincts reporting, Duckworth led with 78 percent of the vote, while Kirk had 17 percent. Statewide, she led with 720,700 votes, or 66 percent of the vote, to Kirk's 318,100, or 29 percent.
The seat was once held by President Barack Obama.
Union leaders congratulated Duckworth. Keith Kelleher, president of SEIU Healthcare Illinois, which represents caregivers for people with disabilities, called the victory historic.
“As the healthcare union that represents caregivers to people with disabilities, it makes us especially proud to welcome Tammy Duckworth as our next U.S. senator," he said. "We know Tammy’s work will be much broader and she will be a fierce champion for the economic security of all Illinoisans, but having someone who understands the issues particular to our workforce and our consumers is historic.
Kirk was one of only two Republicans to represent Illinois in the U.S. Senate in more than three decades.
The Democratic victory in the Illinois race could help the party regain control of the U.S. Senate.
Kirk, from the suburbs north of Chicago, said Tuesday he did not vote for Republican Presidential nominee Donald Trump. Instead, he said wrote in former CIA Director David Petraeus.
However, Kirk criticized Obama harshly during the campaign, at one point telling a newspaper that "we can't have the president of the United States acting like the drug-dealer-in-chief."
Duckworth ripped Kirk as an ineffective senator, while Kirk condemned Duckworth as a tool of the Illinois Democratic machine.
Duckworth spent part of Election Day at Manny's Deli in the South Loop Tuesday.
Duckworth, who had a corned beef sandwich, potato pancake and pickle, told reporters that the election was a major moment for women.
"It's so historic," she said. "What's historic is the fact that the women in each case are the best candidate. You shouldn't vote for them just because they are women, you should vote for them because they are the best candidate."
She said she was impressed that voters were bringing their daughters to the polls to witness history, but "what really warms my heart is they are also bringing their sons out to show them all the women at the top of the ticket."
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