Democrats, whose very relevance in the Trump era depended on winning at least one chamber of Congress, were laser-focused on health care as they predicted victories that would break up the GOP's monopoly in Washington and state governments.
They could also force the President to scale back his legislative ambitions, possibly dooming his promises to fund a border wall with Mexico, pass a second major tax-cut package or carry out his hardline policies on trade.
As for Republicans retaining control of the Senate, she called it "a huge moment and victory for the president".
Democrats seized control of the lower house of Congress in midterm elections.
And Rep. Adam Schiff, slated to become chairman of the House Intelligence Committee, has vowed to probe alleged Trump campaign-Russia collusion.
"We will have a responsibility to find our common ground where we can, stand our ground where we can't", Pelosi said.
Missouri is extremely close for the President, where 51% approve and 48% disapprove and Republican Josh Hawley holds a commanding lead over incumbent Sen.
Tuesday's result was a bitter outcome for Trump, a 72-year-old former reality TV star who campaigned for fellow Republicans on increasingly hostile anti-immigrant rhetoric and was accused of inciting violence in recent weeks.
Most Democratic candidates in tight races stayed away from harsh criticism of Trump during the campaign's final stretch, focusing instead on bread-and-butter issues like maintaining insurance protections for people with pre-existing medical conditions and safeguarding the Social Security retirement and Medicare healthcare programs for senior citizens.More news: Tesla says SEC subpoenaed Mannequin three manufacturing data
The White House has been stressing the historical headwinds it faced: In the last three decades, 2002 was the only midterm election when the party in office gained Senate seats.
There was some consolation for Democrats as Senators Joe Manchin and Bob Menendez held on to their seats after tough campaigns in West Virginia and New Jersey respectively.
Going into the 2018 midterms, the GOP held 236 of 435 House seats; Democrats held 193 seats.
The turning point was when Republican businessman Mike Braun ousted incumbent Joe Donnelly, a moderate Democrat in Indiana.
The Democratic gains could have big effects, soon and longer term.
In the Issaquah-area 5th District, a pair of Republican House candidates - former Rep. Chad Magendanz and current Rep. Paul Graves, R-Fall City - trailed Democratic challengers Bill Ramos and Lisa Callan. They also suffered a setback in Florida, where Democrat Andrew Gillum conceded in his bid to become the state's first African-American governor.
Overall, women voted considerably more in favor of congressional Democratic candidates - with fewer than 4 in 10 voting for Republicans, according to VoteCast, a nationwide survey of more than 115,000 voters and about 20,000 nonvoters - conducted for The Associated Press by NORC at the University of Chicago.
For one-third of IN voters, President Trump was not a factor they considered while casting their votes. "Democrats have a number of paths to the 23 seats they need".
Democrats also captured governorships in Michigan, Illinois and Kansas. The president urged supporters to "pretend" he was on the ballot. Nine GOP and 26 Democratic seats were up for election in the Senate, and 91 GOP and 22 Democrat in the House of Representatives. Two Democratic women veterans with viral web videos - MJ Hegar in Texas Amy McGrath in Kentucky - lost their races in traditionally Republican districts.
Trump had noted the energy as he wrapped up a punishing schedule of rallies around the country that were meant to boost Republican candidates - and his own brand heading towards reelection in 2020. And they would claim subpoena power to investigate Trump's personal and professional shortcomings.
"When we win, on the opening day, our Democratic Congress will be open and transparent", Pelosi said at an event Tuesday morning.