Miguel Almiron has been ruled for the rest of the season after suffering a hamstring injury in Saturday's 3-1 win over Southampton.
The 25-year-old left the field in tears in the 64th-minute before being handed a standing ovation by the St James's Park crowd.
Early signs over the weekend had suggested Almiron's end to the season would be cut short - and those have proven to be right, United's medical staff have confirmed.
That means the 25-year-old will miss this weekend's trip to Brighton and Hove Albion before sitting out the games against Liverpool and Fulham.
Since joining from Atlanta United for a club record £20million, Almiron has transformed the United attack and steered them away from relegation trouble.
His partnership with Salomon Rondon and Ayoze Perez has seen them branded as the 'Three Amigos' - with the latter enjoying a run of five goals in six games.
It comes as a blow for the Magpies fans, who have been left excited by the South American, however can take comfort from the fact they have already secured their top-flight status.
That said, Almiron could still appear ahead of next season, who has hopes of recovering in time for the Copa America in July.
Newcastle confirmed they have been in communication with - and will continue to liaise with the Paraguayan Football Association over Almiron's recovery.