Halfpenny out of Wales' Six Nations opener due to injury
The full-back was due to win his 98th cap in his first start for 19 months in the opening game of Warren Gatland's second spell in charge.
Halfpenny had overcome a serious knee injury to get himself back into contention for selection.
His replacement for the clash against the top-ranked side in the world at the Principality Stadium will be Cardiff's Liam Williams.
"Unfortunately, Leigh had a back spasm this morning and Liam will be playing," said Wales assistant coach Jonathan Humphreys.
"I think it's more disappointing for him as a person. He is an unbelievable professional and an unbelievable person.
"He has got to pick himself up again. You feel for him that he's got to pull out at this late stage."