The move sees Carrillo, 26, joining up again with Saints manager Mauricio Pellegrino, having previously played for his compatriot when they were both with Argentinian side Estudiantes.
No fee was disclosed by Southampton, but British media reports said they had paid £19.2 million ($27.1 million, 21.8 million euros).
It was from Estudiantes that Carrillo joined Monaco in 2015, going on to help the principality club end the domestic dominance of Paris Saint-Germain with their first Ligue 1 title since 2000 last season.
South coast side Southampton are currently in the relegation zone, a point shy of safety, with the Saints in desperate need of goals after managing a mere 24 from as many league games so far this season.
“I’m very happy. It’s a great feeling to be a part of this club,” said Carrillo in a club statement.
“Lots of things attracted me. I know Southampton from watching the Premier League from when I was small, I’ve always regarded it as the most important league in the world.”
He added: “I obviously know the coaching staff, I’ve worked with them in Argentina and I also spoke with some players who were former teammates in Argentina, who are now playing in the Premier League and they told me all about the club and gave it a shining reference. Therefore, I had no doubts when I took the decision.”
Carrillo scored 15 league goals in his two-and-a-half seasons at Monaco, but started only seven times since the start of the 2016/17 campaign.
Southampton vice-chairman Les Reed welcomed Carrillo to St Mary’s by saying: “Guido represents a very exciting addition to our attacking options ahead of the final months of the season, possessing plenty of experience at the highest level, while also having the potential and the desire to improve even further.
“We are confident he will benefit us not only in the remainder of this campaign, but in the years to come.”
Southampton, the 1976 FA Cup winners, are at home to Premier League rivals Watford in the fourth round of this season’s edition on Saturday.
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