Warren Gatland has left his role as Wales head coach by "mutual agreement" after a record run of 14 straight Test defeats, the Welsh Rugby Union announced on Tuesday.
Cardiff coach Matt Sherratt will take temporary charge for the side's remaining three Six Nations games against title favourites Ireland, Scotland and England.
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WRU chief executive Abi Tierney said both parties had agreed an immediate change "is in the best interests of the Wales squad".
"We are grateful to Warren for all he has done for the game in Wales. He remains our longest-serving and most decorated head coach in terms of the silverware he has won," she added.
Gatland was reappointed for a second stint in charge of Wales in December 2022 after winning three Six Nations Grand Slams and reaching two Rugby World Cup semi-finals during his first spell.
The 61-year-old New Zealander said: "I would like to thank the WRU board for the faith shown in me after a tough campaign throughout 2024 and affording me the time and resources to try to turn things around for this 2025 tournament.
"We have worked hard, we have a talented young squad that is developing and have been desperate to turn potential into results but now is the right time for a change."
Wales, who finished bottom of the Six Nations last year with five defeats, are on course for another embarrassing whitewash after a 22-15 loss in Italy at the weekend.
They face a daunting task against two-time defending champions Ireland in Cardiff on February 22 before a trip to Scotland and a home fixture against England.
Gatland's position came under formal review after the November internationals, which featured defeats against Fiji, Australia and South Africa.
Speaking at the time, Tierney said she would "make no secret of the fact that his position was on the line as we undertook our review".
Wales were hammered 43-0 by France in their opening game of this year's Six Nations before their defeat on Saturday, which was their first loss in Rome for 18 years.
The proud rugby nation have slumped to a new low of 12th in the world rankings, below Georgia.
Gatland took over from compatriot Wayne Pivac, returning to a job in which he had enjoyed marked success in his first spell in charge, from 2007 to 2019.
That yielded four Six Nations titles -- including three Grand Slams -- and two appearances in World Cup semi-finals.
Wales briefly occupied top spot in the world rankings in 2019.
Gatland's team registered just one win in the 2023 Six Nations, but the former British and Irish Lions coach led them to the quarter-finals of the World Cup in France later that year, including a 40-6 destruction of Australia.
Wales have not won a Test match since beating Georgia in the pool stages of that tournament, with defeat to Argentina in the quarter-finals marking the start of their miserable run.
Overall Gatland won just six Tests from 26 in charge during his second spell as Wales coach.
He had to work against the backdrop of a threatened strike by players in the early months, linked to a deep financial crisis within the Welsh game.
He has also had to cope with the retirements of a host of experienced players including Alun Wyn Jones, Justin Tipuric, Rhys Webb, Dan Biggar, Josh Navidi, Leigh Halfpenny and George North.
Tierney said the WRU aimed to have a permanent appointment in place before the two-Test tour to Japan later this year "with all options open".
Former Australia coach Michael Cheika, Glasgow's Franco Smith and Ireland interim boss Simon Easterby are reportedly in the frame.
Sherratt said he "couldn't turn down" the chance to coach Wales, though he added he would not be putting his name forward for the full-time role.
The Englishman, speaking at Wales' training base, said he would encourage his players to be "brave".
"It is going to be very difficult to change a huge amount technically and tactically in what will probably be three or four sessions before we play Ireland," he said.