The Saints playmaker started among the substitutes as his national side hosted Colombia in a vital South American qualifier yesterday evening.
Having only won three of their first 11 qualifiers, Uruguay's place at next summer's World Cup had looked in some doubt at the end of last season.
However, recent back-to-back wins over Venezuela and Peru sent them into last night's game in a strong position.
With the game goalless going into the final 20 minutes in Montevideo, Ramírez replaced Cristian Rodríguez and the match soon swung in the hosts' favour.
Edinson Cavani gave Uruguay the lead on 77 minutes, before Ramírez crossed for fellow sub Christian Stuani to wrap things up ten minutes from time and secure a third successive victory.
The result leaves Ramírez and his teammates in the CONMEBOL qualification play-off spot, though only four points separate them from second-place Colombia.
La Celeste's destiny will be decided next month, when they travel to fourth-placed Ecuador before hosting already-qualified Argentina.
If Óscar Tabárez's men end up in the top four they will qualify for next summer's finals, while a fifth-placed finish would see them play off against the fifth-placed Asian team – confirmed to be Jordan – in mid-November.
Ramírez will now head back to Southampton ahead of Sunday's Barclays Premier League home game against West Ham United.