The 35-year-old played 153 times for the All Blacks and won back-to-back Rugby World Cups in 2011 and 2015.
He narrowly missed out on becoming the first player to win three World Cups when New Zealand were beaten by a single point by South Africa in the final in Paris last year.
Whitelock had come on in the 55th minute of the final, extending his own record for World Cup appearances to 26.
After the final, he joined Pau in France’s Top 14 on a two-year contract.
The announcement he is retiring will put an end to speculation that he was set to make a return to Test rugby this year, following a reported approach by new All Blacks head coach Scott Robertson.
“It’s time to finish the playing chapter of rugby,” Whitelock said in an All Blacks statement.
“I’ve been having a few conversations with my wife Hannah and the kids around what the future looks like for us.
“I think if you talk to anyone who has played for a long time, that desire (to compete) never leaves, it’s just that stage of life when you move on.
“It’s not a decision that we have come to lightly, but it’s the right thing for myself and it’s the right thing for my wife and our three kids — Fred, Iris and Penelope.
“And I think that is what excites me the most – spending more time with my kids and my wife, and actually watching them play sport. Being able to go to the cross-country at school and those things.”
Whitelock won his first Test cap in 2010 against Ireland and was the youngest All Black to play in 100 Tests and the quickest in the world to achieve the milestone.
His overall appearance record places him second only to Alun Wyn Jones of Wales on the all-time list of most-capped internationals.
‘An Immortal’
His valuable contribution to the All Blacks’ cause was illustrated in their 28-24 victory against Ireland in the quarter-finals of last year’s World Cup when he achieved a turnover in the 84th minute that sealed victory in what is widely regarded as one of the best games of rugby ever seen.
Robertson, the All Blacks head coach, said: “Sam is an immortal of our incredible game.
“First and foremost, he is a quality person. Sam’s impact has been immense both mentally and physically over four World Cup cycles.
“He is a winner who rose to any occasion as his competitive spirit drove him to the highest level of performance. Sam will stand with the greats of our game.”
Whitelock also played 180 times for the Crusaders, winning seven Super Rugby titles during his time at the club.
At international level, he won 11 Tri Nations/Rugby Championship titles and was involved in 14 straight seasons where the All Blacks retained the Bledisloe Cup.
He played basketball at high school, which helped him develop his exceptional catching skills in the line-out and passing.
He is one of four Whitelock brothers to have represented the All Blacks, playing five Tests together with Luke, two years his junior, who is now his teammate at Pau.
Another brother, George, played one Test for the All Blacks in 2009 and a fourth, Adam, played for their Sevens team.
New Zealand Rugby Chief Executive Mark Robinson hailed Sam Whitelock as “a sounding board for numerous players, coaches, administrators and others” and hinted he could find eventually join the All Blacks’ coaching setup.
“While he’s hanging up his boots, we know he’ll stay involved in rugby one way or another in the future,” Robinson said.
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