The 33-year-old Vancouver Whitecaps frontman won the last of his 69 caps in the 3-2 defeat to England at Wembley last week and signed off with a goal - his 18th for his country.
The former Hibernian, Rangers, Celtic, Wolves and Cardiff striker hangs up his boots with only Kenny Dalglish, Denis Law, Hughie Gallacher, Lawrie Reilly and Ally McCoist ahead of him in the Dark Blues' list of all-time top scorers.
Scotland boss Gordon Strachan said: "Kenny is a talented player who absolutely gave the best of himself when he was on Scotland duty.
"In my time as national coach it has been a pleasure to have a player with his ability and experience in the squad.
"He has come to this decision to help prolong his club career, and feels that this is the best time to bow out.
"We understand his decision and wish him all the best for the future."
Miller was handed his international debut by Craig Brown on April 25, 2001, in a 1-1 friendly draw with Poland but had to wait almost two years for his second cap and first goal for Scotland as he netted in a 2-1 Euro 2004 qualifying win over Iceland.
He struck his second against Germany in June 2003 and also had the Scots - then bossed by Walter Smith - a goal up with a header against Italy in their 1-1 draw during qualifying for the 2006 World Cup.
One of his most memorable strikes came with a swerving 25-yard volley against Cyprus in a Larnaca friendly two years ago.
But even that stunner will have been overtaken by his Wembley goal last week.
The veteran frontman shook his hips one way then the other to leave England defender Gary Cahill in a stir before turning and sweeping a fine finish past Joe Hart to put the Scots 2-1 up.
There was no final moment of glory for the Edinburgh-born player, however, as Danny Welbeck and Rickie Lambert struck to deny the Dark Blues victory in London.
Miller entered the International Roll of Honour in October 2010 after winning his 50th cap in a Euro 2012 qualifier against Czech Republic.
But the departure of a man who has made the lone striker position his own under Brown, Berti Vogts, Smith, Alex McLeish, George Burley, Craig Levein and now Strachan leaves the current Scotland boss with a major headache as he searches for his successor.
Leigh Griffiths will vie with Steven Fletcher and Jordan Rhodes for that honour and the Wolves frontman was quick to pay tribute to his former team-mate.
He tweeted: "Sad to hear about Kenny miller, been a great servant to Scotland for a number of years! So many important goals for Scotland! #topplayer."