She also tried to appeal to the Republican roots in the district by trying to tie Ossoff to national Democratic bogeymen like House Minority Leader Nancy Pelosi (D-CA), while Ossoff, for his part, went after Handel over her time at the Susan G. Komen Foundation.
Those trends leave Democrats hopeful they can win a House majority next year.
In Ossoff, Democrats had an attractive 30-year-old political newcomer who quickly attracted national attention-and Democrats and Republicans dumped over $50 million in the race, making it the most expensive House contest in the nation's history.
The seat had been vacated by Tom Price when the former congressman joined Trump's cabinet to become secretary of health and human services and previously held by Republican stalwarts like Senator Johnny Isakson and former speaker Newt Gingrich.
The race was called for Handel around 10:15 p.m. Tuesday.
The district spans affluent and increasingly diverse suburbs north of Atlanta.
It was enough to help Handel raise more than $5 million, not a paltry sum in a congressional race, but barely a fifth of Ossoff's fundraising haul.
Handel told about 200 supporters: "Y'all rock".
The defeat on Tuesday is a symbolic blow to the Democrats' momentum heading into 2018, when they're looking to pick up 24 seats to retake the House.
Georgia's sixth district is a traditionally safe Republican seat but Democrats had hoped to capitalise on the President's low approval ratings, the BBC reported. Seth Moulton, a democratic congressman from MA echoed the thoughts of many, tweeting: "Race better be a wake up call for Democrats - business as usual isn't working".
Georgia is not the only special election that happened Tuesday.
The Georgia race isn't the only special election happening Tuesday, though. They will have to run harder and will be winning more narrowly, he said.
Handel will soon have to defend the seat for the 2018 midterm elections.
Trump won the highly-educated Georgia 6th District by only 1.5 points previous year.
State officials said polling places at Livsey Elementary School and Holy Cross Catholic Church received the wrong equipment for checking in voters.
Ossoff announced his concession to Handel in remarks to his supporters in Atlanta.
Earlier in the day, Handel appeared at her polling place to mock Ossoff for the fact that he doesn't even live in the district, and can not vote for himself.
That would contrast with last April, when Fulton County could not report vote totals for several hours after polls closed in the special election in Georgia's 6th congressional district.
If Handel were to win, Republicans on Capitol Hill could feel they are on the right track - helping the GOP's push for health care and tax reform legislation.
"Winning in Georgia 6 - a district that hasn't elected a Democrat in three decades - was always an uphill battle", said Rep. Joe Crowley (D-NY), a top House Democrat. Workers had to use paper lists as a backup. The president had increasingly tweeted about the race in the run-up to election day.
Democrats have lost every special Congressional election since President Donald Trump took office.
Handel, meanwhile, just needed to bring home a respectable number of people who spent years voting for Mitt Romney, John McCain, and the dozens of other GOP candidates before Trump came along.
Ossoff grew up in the district but now does not live there.
Mrs. Handel, a former secretary of state, was declared the victor by networks and the Associated Press more than three hours after the polls closed at 7 p.m., overcoming a well-financed challenge from Democrat Jon Ossoff in the most expensive U.S. House race in history.