Silva made his global debut in November 2006 and went on to amass 125 caps over the course of 12 years, scoring 35 times for La Roja, a total that places him fourth on the all-time list for his country behind Fernando Torres, Raúl and David Villa.
The 31-year-old made the last of his 102 worldwide appearances in Spain's World Cup last-16 loss to Russian Federation.
After Gerard Pique confirmed his retirement from global football, another Spain World Cup victor has announced his retirement from the national side.More news: Sergio Ramos continues Klopp feud with biggest dig yet
Silva will now focus on prolonging his club career at City; he found the net nine times to help Pep Guardiola's side secure the Premier League title last season.
"It's not easy to write this after all that I have experienced.
It has been days and weeks of reflection and analysis to take the decision to end my era in the Spanish national team", wrote Silva in an open letter on his Twitter account on Monday. Without a doubt it is one of the hardest decisions in my career'.More news: 21-year-old woman becomes youngest in United States to receive face transplant
David Silva has scored 35 goals in 125 games for Spain.
"I can not leave without thanking all of my team-mates, the coaches that had faith in me and the RFEF employees that do everything to make our lives easier".
The 32-year-old expressed gratitude to his teammates, the coaches of the national team and the Spanish soccer federation officials, who he said have been keen to make things "easier" for the players. And of course, the fans who have always given me their support and respect every time I wore the Spain shirt.More news: Rooney inspires DC United to last-gasp win
Andres Iniesta revealed minutes after July's penalty shoot-out defeat he was standing down, while Gerard Pique followed his former Barcelona captain's example on Saturday during a press conference.