US President Donald Trump has suffered a humiliating defeat after a massive swing against the Republican Party in a byelection in the Trump rust belt base of Pennsylvania.

Coming just three months after the Republicans lost a Senate race in the conservative fortress of Alabama, the GOP suffered another shock loss to the Democrats in a special Congress election in a district of Pennsylvania.

The Democrat candidate, Conor Lamb, 33, held a razor-thin, 627-vote lead by Thursday afternoon (Australian time) over Republican candidate Rick Saccone, 60.

But The New York Times noted that with the votes in remaining districts and provisional and absentee votes totalling only around 500, Mr Lamb’s victory looked almost assured.

The Democrat victory is monumental, given that Mr Trump won the district with a 20 percentage point margin in the 2016 presidential election.

The patchwork of small towns, farms and suburbs of Pittsburgh that make up Pennsylvania’s 18th congressional district is so Republican that Democrats did not even bother to field candidates in the previous two US congressional elections.

The loss sent shockwaves through Republican ranks, with Republican Speaker Paul Ryan labelling the defeat a “wakeup call” in a meeting with Republican House members, while The New York Times reported that “Republicans are on edge” after the result.

“It also emboldened Democrats to run maverick campaigns even in deep-red areas where Republicans remain bedevilled by Mr Trump’s unpopularity,” the paper reported.

Republicans are petrified that the result could be a predictor of a wider Democrat momentum that could see the party retake at least one of the houses of Congress in national midterm elections in November.

Bruce Wolpe, a former staffer to president Barack Obama, said the key factor that upended the Republicans’ dominance in Pennsylvania was the character of the President whose approval was in the “death zone” of below 50 per cent.

“What has happened in Pennsylvania – which has been evident for some time but with no outlet for expression until today – is a huge disconnect between a solid economy, with hope for the future, and the President who is leading it,” Mr Wolpe wrote for the ABC.

“The former is heartily welcomed, but Mr Trump himself is viewed with deep concerns about his character and how he conducts his duties. And the Republican majorities in Congress are now in danger of falling into that gap.”

President Trump with candidate Rick Saccone at a rally last weekend. Photo: Getty

Mr Trump held two events in the district during the campaign, including a high-profile rally on Saturday. But even the announcement of tariffs on imported steel – which was expected to appeal to voters in a state reliant on its steel industry – appeared to have little bearing on Republican fortunes.

Mr Lamb, 33, a US Marines veteran, was described by one Republican as “more like a Republican” than a Democrat, and interestingly distanced himself from his party’s leaders as well as taking a more conservative position on gun control.

The Republican candidate, Mr Saccone, a former Air Force counter-intelligence officer, had described himself as “Trump before Trump was Trump” and led the race by more than 10 percentage points in January.

Mr Saccone has said he may still contest the outcome, while the party itself was conceding nothing and had not ruled out a recount.

The final outcome may not be known until Saturday (Australian time).

-with AAP