Pique did not immediately confirm his retirement following Spain's exit from the World Cup, when they lost on penalties to hosts Russian Federation in the last 16.
Pique had declared his intention to quit worldwide football after the 2018 World Cup following a qualifier against Albania in October 2016, when he said he was exhausted of criticism and wanted "to be left in peace".
And despite the presence of former Barca boss Luis Enrique on the Spain bench, Pique has made a decision to call it a day.
Only 12 other players have 100 appearances or more with Spain's national team.
NASA's flight to sun delayed by last-minute technical issues
Thousands of people had gathered at Cape Canaveral to watch the take-off, which was initially due to take place at 4.38am local time.
Enrique took over as coach after the World Cup last month, which saw Fernando Hierro in temporary charge following the shock sacking of Julen Lopetegui on the eve of the tournament.
Pique is the latest member of the great World Cup-winning Spanish side to quit the national team, following the likes of former Barcelona teammates Xavi Hernandez and Andres Iniesta.
He also played a key role in Spain's 2010 World Cup and 2012 European Championship success.
"Playing for Spain was an awesome experience, and I was able to win the World Cup and the Euros". "Now I want to focus on Barça". 'I have a few years left here and I'm going to enjoy them a lot'.