The Australian has ended his short dalliance with American football to try to win a place in Fiji's rugby sevens squad for Rio 2016.
He played eight games in his only season as a running back with the San Francisco 49ers, but the lure of the Olympics has proved too strong.
"I am retiring from the NFL because the Fiji rugby sevens team reached out to me about the opportunity to join the team for the upcoming Olympics, and I simply could not pass that chance up," the 28-year-old dual passport holder said in a statement.
"The Olympics has been something I have admired since I was a little boy, and it is an opportunity I feel very similar to me joining the NFL."
Sydney-born Hayne, whose father is Fijian, has represented both Australia and the Pacific Island nation in the 13-man rugby league code, winning the World Cup with the Kangaroos in 2013.
He signed a three-year deal with the 49ers in March 2015 and made his debut in week one of the new season, though he was waived in late October before returning to the 53-man roster at the end of December. He finished the season with only 17 rushing attempts and six receptions.
"The past 12 months with the San Francisco 49ers have been absolutely incredible. I could not have predicted how far I have come as an NFL player," Hayne said.
"To not only be able to play in a game but also say that I started a game in the NFL is something that I will remember for a lifetime."
Hayne has joined up with the Fiji team in London for this weekend's final event of the 2015-16 Sevens World Series, which it leads by 14 points, and was named in the squad Friday as a late injury replacement.
"I think with the Olympics coming up, and also the curiosity to playing the game, being half Fijian it is something I've followed since I was a kid," Hayne told reporters.
"My Dad is Fijian and we watched a lot of Serevi games, and William Ryder was a big idol of mine. I have always dreamed about playing sevens for Fiji and I've been given the opportunity.
"It is a team that plays with a lot of spirit and a lot of faith. You don't really see that in teams around the globe. I've played for many different teams at the highest level and Fiji is a special nation and a special country to play for."
Coach Ben Ryan said he could make "no promises" that Hayne would secure a place in his 12-man squad for Rio, where Fiji will seek to win its first Olympic medal in any sport.
"It is a huge challenge for Jarryd but if he gets into the squad it is only going to be on form, because he is a blinding rugby player. If he doesn't make it, is just shows how good this Fijian sevens side is," the Englishman told the Fiji Rugby Union website.
"It is a 'no lose' situation for me. It is 'no lose' for Jarryd -- he gets himself into the possibility of being a part of this journey, and the boys are all going to learn off him as well. He comes in with an A* but it is up to him to hang onto that -- it's really exciting and really what the Olympics is all about."
Hayne is one of several sevens converts hoping to go to Brazil, where the shortened format makes its Games debut.
He attended February's Sydney Sevens, where Wallabies star Quade Cooper joined up with Australia's squad but did not feature at the tournament
. Though he played at subsequent events in Las Vegas and Vancouver, the Toulon back will not be considered for Olympic selection.
American Nate Ebner, meanwhile, put his career with 2015 NFL champion New England Patriots on hold to join the U.S. sevens squad.
There had been doubts Hayne would be eligible to compete in Rio, with reports claiming that anti-doping regulations require athletes to be involved in WADA's drug-testing program for a set period of time.
However, sevens' governing body World Rugby confirmed he can take part, as those rules don't apply to players selected at international level for the first time, and he will be included in its pre-Rio 2016 risk-based testing program.
WADA told CNN that Hayne's case met its rules, and that a six-month rule applies only to athletes returning to a sport after retiring; rugby league is considered separate to rugby union.
Meanwhile, Argentina XVs star Juan Imhoff will also press his claims for an Olympics place at the London finale.
The 28-year-old winger, who scored five tries at the 2015 Rugby World Cup as the Pumas reached the semifinals, has been released by French club Racing 92 after playing in last weekend's European Champions Cup final defeat against Saracens.
Argentina, coached by all-time sevens record try-scorer Santiago Gomez Cora, finished fourth at last weekend's Paris Sevens -- where Samoa shocked Fiji in the final.