The Bath back-rower, who has won 72 caps for Wales and has played in four Tests for the British and Irish Lions, will need surgery.
“Taulupe Faletau has been ruled out of Rugby World Cup contention due to a clavicle injury,” the WRU said in a statement on its website.
“The injury was sustained in an innocuous training ground incident and will require surgery. A prognosis and return to play time-frame will be established after surgery.
“The Wales squad and management would like to wish Taulupe the very best with his recovery.”
It is the latest cruel injury setback for 28-year-old, who broke his arm twice last season and has not played for Wales since March 2018.
But he has trained with Wales this summer and was recently part of an intensive two-week camp in the Swiss Alps as he built towards potential World Cup selection.
Only last month, Faletau spoke about his hunger to play again after being sidelined for so long.
His absence will be keenly felt, although Wales have considerable back-row resources with Ross Moriarty, Josh Navidi, Aaron Shingler, Justin Tipuric and Aaron Wainwright among those in head coach Warren Gatland’s training squad.
Gatland is due to name his final 31-man World Cup squad in early September, with Wales’s opening game being against Georgia in Toyota City on September 23.
Bath director of rugby Stuart Hooper told the club’s official website: “Any time a player misses out on a major competition is hugely disappointing.
“We are all feeling the impact of this news, especially as it follows a number of unfortunate and frustrating injuries for him.
“We will plan and support Toby’s (Taulupe’s) recovery, making sure it is the very best for him, in order to maximise his successful return to the game.”