With much of the vote counted, state Rep. Katie Arrington was on the cusp of winning outright.
Sanford was defeated by state Rep. Katie Arrington, who spent her campaign blasting Sanford a "Never Trumper".
In South Carolina, former governor Mark Sanford, who rehabilitated his image after a freakish scandal some years to get elected to Congress, was a surprise loser in his primary after President Trump came out against him.
The congressman had been a rising star in the GOP in 2009 when his aides told reporters he was missing because he was hiking the Appalachian Trail - only for him to get caught instead returning from Argentina, where he had been visiting his mistress.
Sanford is the second incumbent House Republican to lose a primary this year, though the defeat of Rep. Robert Pittenger in North Carolina came despite his staunch support for the president.
South Carolina Republicans expressed their discontent during primary voting Tuesday as President Donald Trump sought to influence the race. Her statement rings true for several primary races happening this year where Republican candidates either declare their undivided support to the president or risk losing elections. Alabama Rep. Martha Roby was forced into a runoff.
Trump took a victory lap on Wednesday, saying on Twitter that he was urged by advisers not to get involved in the primary, but "Sanford was so bad, I had to give it a shot".
In an interview with Politico last weekend, Sanford suggested that a loss in his re-election bid could cause other Republicans to think twice before speaking out against the Trump administration.
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"Why don't we just start to say it has devolved into a cult?"
While fealty to the Republican president may be a requirement to win low-turnout Republican primaries dominated by conservative activists, it could prove a tougher sell against energized anti-Trump Democratic forces in midterm elections this fall. Nevada, North Dakota, Maine and Virginia also chose candidates for the midterm election on November 6, when Democrats hope to capture a majority of the U.S. Congress. "He is MIA and nothing but trouble", Trump wrote. "He is better off in Argentina".
As voters made their primary choices in five states, SC wasn't the only place where Republicans favored conservatives who are seen as closely tied to Trump and his agenda. In his remarks Tuesday night, he said: "I stand by every one of those decisions to disagree with the president".
"I am extremely disappointed that a candidate like Corey Stewart could win the Republican nomination for US Senate", former Virginia Republican Lt. Gov. Bill Bolling tweeted.
The drama evaporated from both races after direct intervention from Trump and his political team to convince Cramer - who'd already publicly said he wouldn't run - to change his mind and launch a campaign in February.
In Sanford, he chose a well-known former governor, who among other criticisms held him partly responsible for a shooting at a congressional baseball practice by stoking national tensions.