The musician backed the South American side in the final of the international football tournament, but lost it all after Spain's 1-0 victory in extra time on Sunday.
The 39-year-old put his money behind the South American team on Saturday through the betting site Stake, and could have had a payout of more than $US5.1 million ($A7.3 million).
Over the years the so-called Drake curse has seen a series of defeats for sports teams and athletes photographed with or bet on by the artist.
It comes days after he lost a $US1 million ($A1.4 million) wager on Irish fighter Conor McGregor winning his UFC bout against Max Holloway.
A website named TheDrakeCurse.com has even been created to log his full sports betting history.
Born Aubrey Drake Graham, the 39-year old Canadian rapper is known for songs including One Dance, Passionfruit and Hold On, We're Going Home.
The five-time Grammy winner released three new albums - Iceman, Maid Of Honour and Habibti - all at once in May.
They were his first releases since 2023, and secured Drake his seventh number one album on the UK album chart with Iceman.
He was previously at the centre of a headline-making feud with US rapper Kendrick Lamar, as the American musician insulted Drake in the diss track Not Like Us.
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