Moore's win is sending shockwaves through the GOP establishment -- including at the White House, where President Donald Trump had poured his own political capital into helping Strange survive.
At his victory party, Moore said he'd spoken Tuesday night with Sens. Mike Lee of Utah, Rand Paul of Kentucky and Ted Cruz of Texas. He also offered a national audience a glimpse of his religious-themed rhetoric.
"We have to return the knowledge of God and the Constitution of the United States to the United States Congress," Moore said.
"I believe we can make America great, but we must make America good," he said. "And we cannot make America good without acknowledging the sovereign source of that goodness ... which is almighty God."
With 100% of precincts reporting, Moore had 54.6% of the vote to Strange's 45.4%, according to the Alabama Secretary of State's office.
Strange conceded shortly after 8:30 p.m. local time, 9:30 p.m. ET.
"I am especially grateful for the support of President Trump and Vice President Pence, as well as the strong example set by my friends Richard Shelby and Jeff Sessions. I congratulate Roy Moore on the result this evening," Strange said in a statement. "May God be with him and may God continue to bless Alabama and the United States of America."
Trump, who campaigned for Strange last week and has tweeted in support of his candidacy, congratulated Moore on Twitter.
"Congratulations to Roy Moore on his Republican Primary win in Alabama. Luther Strange started way back & ran a good race. Roy, WIN in Dec!" he tweeted
Moore later tweeted that he spoke to Trump, who endorsed his opponent, after his victory.
He tweeted, "Great to talk with President Trump tonight about #ALSen! I very much look forward to working with the President to win in December!"
A source familiar with the call confirmed they spoke, saying Trump congratulated Moore on the victory. The President tweeted
Wednesday morning that Moore "sounds like a really great guy who ran a fantastic race."
Moore's victory sets the stage for a spate of intra-party bouts in 2018's midterm elections. Already, conservative outsiders in Nevada, Arizona and elsewhere say they see in Moore's win a roadmap they can follow. And, like Moore, they have support from Steve Bannon
, the former Trump White House chief strategist who has portrayed the contests as rebukes of Senate Majority Leader Mitch McConnell and congressional leadership that has failed to enact Trump's agenda.
Moore now faces Democratic nominee Doug Jones in a December general election in the race to replace Sessions.
Moore's win Tuesday night will thrust his long history of homophobic
and racially tinged remarks into the spotlight.
He has campaigned on a platform of placing Christianity at the center of public life. In 2003, Moore was removed as state Supreme Court chief justice for refusing to take down a Ten Commandments monument. He was re-elected to the job, and then ousted again in 2016, when he refused to follow the US Supreme Court's ruling legalizing same-sex marriage.
Though Alabama is a solidly red state, Democrats hope Jones, a former federal prosecutor who rose to prominence by leading the government's case against two perpetrators of the 16th Street Baptist Church bombing, can make the race competitive. Former Vice President Joe Biden plans to visit Alabama to campaign with Jones on October 3.
"After years of embarrassing headlines about top public officials in this state, this race is about the people of Alabama and about choosing a candidate with character and integrity they can be proud of," Jones said in a statement after Moore's win was announced. "I will never embarrass the people of Alabama. I am running so the people of Alabama can be proud of their next senator."
Moore overcame a barrage of negative television advertisements from forces aligned with McConnell.
Steven Law, the president of the McConnell-aligned Senate Leadership Fund super PAC that spent $10 million against Moore, said he "won this nomination fair and square and he has our support, as it is vital that we keep this seat in Republican hands."
Moore and his allies persistently bashed McConnell, accusing him of attempting to buy a Senate seat.
"They think you're a pack of morons. They think you're nothing but rubes," Bannon told Moore's supporters at an election eve rally in Fairhope.
But it was Strange's association with another controversial figure, former Gov. Robert Bentley, that left him damaged from the outset of his February appointment.
The appointment of Strange, then Alabama attorney general, came just before Bentley was ousted amid a sex scandal. That tinge of scandal tainted Strange, and both Moore and Rep. Mo Brooks, who finished third in the August primary and didn't make the cut for Tuesday's runoff, and cast Strange's appointment as corrupt.