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Rep. Kevin Cramer of North Dakota, Indiana businessman Mike Braun and Missouri Attorney General Josh Hawley, all staunch Trump allies, won seats held by Democrats. Rep. Marsha Blackburn, another Trump loyalist, defeated a popular former governor for an open seat in Tennessee.
The results held implications for coming battles over the federal judiciary, trade, health care, government spending and immigration. Trump's worldview is expected to be reflected strongly in those debates in the wake of Tuesday's elections.
The outcomes also held significance for Trump himself. His administration could face an onslaught of investigations beginning next year. Democrats took over in the House. Some Democrats have even raised the possibility of impeachment. Senate Republicans could be Trump's bulwark on Capitol Hill.
Trump and Senate Majority Leader Mitch McConnell, R-Ky., spoke Tuesday night, according to McConnell spokeswoman Antonia Ferrier. "The leader and the president had a great conversation, and he thanked the president for all his help," she said.
The Senate Democratic caucus, meanwhile, is poised to shift to the left. The ouster of key centrists willing work with Trump and the presence of several liberal senators gearing up for possible presidential runs could cause more polarization in the chamber.
With the map in their favor, Republicans - who currently control both chambers of Congress - were on track to preserve and possibly expand their 51-to-49 advantage in the Senate. Analysts across the political spectrum had favored them to remain in power, even as they said Democrats were likely to wrest control of the House.
"I see two things," said Jim Manley, a former top Democratic Senate aide, looking ahead. "A president unwilling to tone down his rhetoric, along with the Senate Republicans unwilling to break with him."
Some of the most closely watched Senate races pitted centrist Democrats against conservative Republicans who ardently embraced Trump. Contests in Missouri, North Dakota, Indiana, West Virginia and Tennessee fell into this category.
Even before Tuesday's vote, Senate Republicans were poised for a more pro-Trump roster next year. Sens. Jeff Flake, R-Ariz., and Bob Corker, R-Tenn., who have frequently voiced concerns about Trump's tone and his governing philosophy, are retiring. John McCain, a vocal Trump critic, died in August.
Democrats tried to defeat candidates who marched in lockstep with Trump by running on preserving health-care protections and other so-called "kitchen table" issues. In key races, they fell short.
In North Dakota, Cramer's defeat of Sen. Heidi Heitkamp means that one of the chamber's few moderate Democrats will be replaced by a close ally of Trump. Trump personally recruited Cramer to run. On major issues, Cramer endorsed Trump's positions.
In Indiana, Braun ran in Trump's mold, as an outsider eager to shake up Washington. He defeated a pair of House members in the Republican primary before beating centrist Democratic Sen. Joe Donnelly on Tuesday.
Two states over in Missouri, Hawley ousted Sen. Claire McCaskill, D, in a race with similar dynamics. Hawley, like Cramer, championed Trump's views on trade, even as he faced criticism that farmers in his state would suffer under the president's tariffs.
One wild card next year is Mitt Romney. The former Republican presidential nominee won the seat of retiring Sen. Orrin Hatch, R. Romney has criticized Trump, including in a speech opposing his candidacy in 2016. But lately, he has been less openly hostile to the president.
Senate Democrats were defending 26 of the 35 seats on the ballot, including 10 in states Trump won. They were hoping to offset their losses with some gains.
They looked to pick up a pair of seats in the Sun Belt, with Rep. Jacky Rosen, D-Nev., trying to unseat Sen. Dean Heller, R, a onetime Trump critic who warmed up to the president during the campaign.
In Arizona, Democratic leaders were hopeful that Rep. Kyrsten Sinema, a former Green Party activist who ran as a moderate Democrat, would win Flake's seat. Her opponent was Rep. Martha McSally, a onetime Trump critic who dialed down her hostility in the campaign.
Florida, another state with a diverse population, was the site of the expensive and pivotal showdown between Sen. Bill Nelson, D, and Gov. Rick Scott, R. Scott, unlike most other top Senate candidates, distanced himself from the president in the campaign. The race was tight late Tuesday.
Many Democratic Senate contenders railed against Trump's tariffs during the campaign. In Tennessee, former governor Phil Bredesen, who lost to Blackburn, cast the tariffs as harmful to the state's automobile, farming and whiskey industries.
Sen. Joe Manchin III, D, held on to his seat in West Virginia. Manchin was the only Democrat to vote to confirm Supreme Court Justice Brett Kavanaugh. He has touted his cooperation with the president, and Republicans are expected to court his support in future votes.
Democrats were hopeful Jon Tester, D-Mont., would keep his seat, despite Trump holding a rally in his state in the final stage of the campaign.
Sen. Ted Cruz, R-Texas, who clashed sharply with Trump in the 2016 primary, lined up squarely behind the president en route to his defeat of Rep. Beto O'Rourke, D, who achieved rock-star status on the left.
The Senate Republican agenda is not expected to be nearly as ambitious as the past two years, when the GOP controlled the federal government following Trump's surprise win. The Democratic House takeover will probably be a major impediment to reaching an agreement on most big issues.
Still, the Senate will have to navigate some high-stakes battles. The Trump administration is preparing for a massive post-midterm shake-up, which could trigger nominations for attorney general and other Cabinet posts the Senate would be tasked with confirming in the months ahead.
McConnell has made confirming federal judges a top priority. That is a task carried out by the Senate alone, and McConnell's allies said that will continue to be a focal point in the next Congress.
"I think that the one thing that becomes really important, both to the administration and Senate Republicans, is to continue to be in the personnel business," said Josh Holmes, a former McConnell chief of staff and one of his closest confidants. "I think remaking the judiciary is high on the agenda, no matter what."
A looming debate over health care and the outcome of a Republican lawsuit against the Affordable Care Act could prompt further consideration of tweaks to the law. Immigration, which Trump and the Republicans made a centerpiece of their midterm pitch, could spark a new debate about border security funding.
Congress will also have to approve or reject a sweeping trade deal Trump spearheaded with Mexico and Canada. More basic tasks such as funding the federal government have proved to be politically challenging in recent years and could be further complicatedby an ideological shift on Capitol Hill.
What voters decided Tuesday also will determine the starting point for the next fight for the Senate majority, in 2020. Republicans are facing a more difficult Senate map, with seats to defend in the purple states of Iowa, North Carolina, Colorado and Maine.
McConnell, who is also up in 2020, was hoping to pad the slim GOP cushion going into the next cycle. The looming races could also be a factor leading some GOP senators to distance themselves from Trump next year.
But Republican senators are still facing the threat of drawing a primary challenger if they are too hostile to Trump. Most party strategists have concluded that straying from him sharply out of the gate would be politically unwise.
One race that did not conclude on Tuesday was in Mississippi. The special election to succeed retired Republican Thad Cochran headed to a runoff on Nov. 27.