He made all his formative years at Vélez Sarsfield and it was at this club that Otamendi made his debut as a professional player, on May 10, 2008.
In 2010, he emigrated for the first time to play in Portugal and at FC Porto. Otamendi moved to Valencia after the closing of the 2013/14 Winter transfer window in Europa, which is the reason why he was loaned to Atlético Mineiro, from Brazil, for six months. He returned to Spain, and a season at Valencia was enough for the central defender to draw the attention of Manchester City.
He is a senior international with Argentina and his debut was sponsored by star Diego Maradona. For “La albiceleste”, he played in the 2010 and 2018 World Cups and 2015, 2016, and 2019 Copa América.