At a press conference, Smith said it was the difficulty returning to the Storm after playing State of Origin that led to his decision.
Cameron Smith has announced his retirement from representative rugby league with immediate effect.
Smith said it was the "right time" to exit the representative arena.
It means Queensland will have to appoint a new captain and hooker for the Origin series opener against New South Wales on June 6.
Smith, the most-capped Maroon of all time, leaves a giant void in the Maroons side at hooker; a position he's had locked down in the Queensland side since 2003.More news: Poor People's Campaign March Leads to Arrests in Montgomery
Smith admitted the lure of playing one last Origin game on the MCG and Suncorp Stadium made him think twice about playing on but in the end "the reasons for not playing outweighted the reasons for playing on".
"Looking back on it now I don't think that it is fair on myself, I don't think it's fair on my family and also my teammates back here at Melbourne Storm".
His departure follows Johnathan Thurston and Cooper Cronk's retirements previous year from the representative level.
Smith, who retired from representative football, would be among the leading contenders after the state's premier called for league fans to nominate the next player to be immortalised like Wally Lewis, Arthur Beetson and Darren Lockyer.
"Not only did they make me a better footballer and a better captain but a better person overall as well", he said.More news: Goalkeeper Ederson commits future to champions Man City
He hopes avoiding tours and extra duties will help him attend more family events with his wife and three children while also resting more.
The 34-year-old didn't rule out taking on the job if it was offered, but said he would leave it in the hands of Queensland coach Kevin Walters.
Walters said it was fitting Smith's final Origin appearance in 2017 was one to remember.
Slater however looks more likely an option than Brisbane's Darius Boyd or North Queensland's Matt Scott.
"I think I've only played one Origin without Cam so it's going to certainly be different".More news: Andy Samberg wants celeb fans to guest star on 'Brooklyn Nine-Nine'