Labour candidate Michael Shanks won the Rutherglen and Hamilton West seat after securing more than twice the votes of his SNP rival Katy Loudon.
The result will pile more pressure on SNP leader and Scottish First Minister Humza Yousaf - who has seen his party's fortunes decline in the polls in the wake of the ongoing police investigation in SNP finances.
The by-election was called after a recall petition against Margaret Ferrier, who had won the seat for the SNP in 2019 with a majority of 5,230.
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