His decision was announced 30 minutes after the RFL confirmed former Wigan Warriors boss Shaun Wane as England head coach on a two-year contract.
A statement from the governing body said Sinfield, who was instrumental in creating the performance unit in his role as the RFL rugby director, will "now stand down to allow the RFL to follow a new direction as the national teams prepare for the 2021 World Cup".
Sinfield, who has also left his rugby director role, said: “I am immensely proud of the progress we have made with all three of our senior national teams.
"In 2018, the England men’s team won four out of five Test matches in the calendar year, winning a series for the first time in over a decade and we saw the re-emergence of the Knights team as a pathway to the national side.
"England Women toured Papua New Guinea in 2019 for the first time with the team being paid in another groundbreaking step whilst our Wheelchair team are amongst the favourites for next year’s World Cup after a strong tour to Australia last year.
“Having reached the 2017 World Cup Final with our men’s team, I was confident we could build on that success in the four-year cycle to a home World Cup in 2021.
"The event will be the greatest tournament our sport has ever hosted and it was my belief that the performance unit was best placed to give all our teams, and especially the men’s team, the chance to end our long wait to lift silverware.
“On a personal note, I would like to thank all the staff and players who have worked so hard on all the six England programmes during my time at the RFL. Our aim was to put the national teams at the pinnacle of our sport in terms of preparation and development, which I believe we have gone a long way towards achieving."
Sinfield's announcement was made 30 minutes after Shaun Wane was confirmed as the new England coach, replacing Wayne Bennett.
Sinfield, who conducted a review into Great Britain's disastrous performance on last autumn's tour to the southern hemisphere, added: “I would particularly like to pay tribute to Wayne Bennett as England head coach.
"Wayne has always shown nothing but complete commitment to the England cause during his time in charge of the national team and the wealth of knowledge he has given to our players and coaches will enhance the game in this country for many years to come.
"His passion for this group of players to succeed in a home World Cup was evident every time I spoke to him about his players and I know it will be a disappointment that he cannot complete that journey with them.
"I am certain, like me, he will wish the team every success in the future as they look to fulfil their undoubted potential.”
Ralph Rimmer, the RFL chief executive, said: “For the last two years especially, but well before that, it has been an absolute pleasure to work closely alongside Kevin, who has always provided outstanding leadership, commitment and guidance to the EPU.
“We’re obviously very sad about Kevin’s decision to step down from his role at the RFL and the England Performance Unit. We did try to convince him to stay, but he has made his decision, and every one of us at the RFL wish him the best in what we’re sure will be a hugely successful future.
“The principles behind the formation of the EPU remain firmly in place, and we’re in a strong place to continue everything we’ve all been working towards.
"I'm grateful to Kevin for his kind words wishing our England teams success for the next two years. In anything we do achieve, his role will always be acknowledged and appreciated and he will remain very much a part of our RLWC2021 journey.”
Meanwhile, Wane - who won three Super League titles, the Challenge Cup and World Club Championship during his spell as Wigan coach from 2011-2018, will take charge of England for this year's Ashes series and the 2021 World Cup.
He has returned to rugby league after spending last year as high performance coach for Scottish Rugby.
Wane, who had a brief spell as a Leeds player in the 1990s, said: “I am honoured to be appointed head coach of my country’s national team at such an exciting and important time for rugby league in England.
“We have a three-Test Ashes series against Australia this autumn, and after that we host the World Cup in 2021.
“Everyone who knows me knows that I’ve always loved the game of rugby league and been proud of British rugby league.
"I’m looking forward so much to starting work with the outstanding rugby league players we have in this country - and also the guys who have enjoyed success in Australia in recent years - to do all we can to win the World Cup next year. ”
Rimmer described Wane as "an exciting appointment that will be welcomed by England rugby league supporters as we prepare for this year’s Ashes series, and the 2021 Rugby League World Cup".
He said: “Shaun is passionate about the game and his country and also an outstanding coach, as shown by his record in eight seasons as Wigan’s head coach, a major feature of which was the success he and the club had in developing so many homegrown players.
“With two years to go in the lead up to RLWC2021, a full review was always programmed in to follow from the 2019 Great Britain tour of New Zealand and Papua New Guinea.
“After careful consideration of the review report, the RFL board concluded that a change of direction on the position of head coach was the next evolution alongside adopting several of the recommendations made.
“We are confident that one of the benefits of Shaun’s appointment will be to further build support for and belief in the national team from the rugby league community and know he will work closely with the clubs within this process."
Rimmer added: “I’d like to place on record on behalf of the RFL and England and Great Britain Rugby League our thanks to Wayne Bennett for his immense contribution as our head coach over the last four years, when England reached the 2017 World Cup Final and had an excellent home series win against New Zealand in 2018.
“Wayne is a very special coach and has taken us on a great journey. Once you see him operate up close then it becomes clear why he has been so successful, and each of our players who have experienced that will have benefited hugely – as have I.”