Higuain has spent the last two years with Inter Miami after leaving Juventus.
The 34-year-old has been in good form for Miami this season, scoring 14 goals in 26 games but feels it is the right time to hang his boots.
Miami currently occupy the final playoff spot in the Eastern Conference with two games remaining.
“The day has come to say goodbye to football,” said Higuain at a press conference.
"Three or four months ago I told the club, it wasn't from one day to the next. I had been working on it for years.
"When I came here, I came for the pleasure of enjoying football, of my life, of having Fede close, my brother. It was another stage in my career, but I can tell you that it was one of the best moments of my career, and this club, my team-mates and the coaching staff gave it to me, who gave me back the desire to play football.
"I can now retire as I always dreamed, scoring goals and having fun playing the game."
Higuain started his career in his native Argentina with River Plate before going on to enjoy stints with Real Madrid, Napoli and Juventus. He also had short spells at Chelsea and AC Milan towards the end of his European journey.
Higuain won three La Liga titles with Real Madrid and three Serie A titles with Juventus. He was also part of the Chelsea side that won the Europa League in 2019.
Higuain also won 75 caps for the Argentina national team, scoring 31 goals.