It is believed to have been taken from Fortingall Church, near to Aberfeldy, sometime between Sunday September 3, and Friday.
The distinctive artefact had been in the possession of the Fortingall and Glenlyon Church for about 1,200 years.
Reverend Anne Brennan said: “We are all just really upset that somebody would take something of such historical value.
“It’s got no monetary value, but in other ways it’s completely irreplaceable, not just for the church but for the whole area.
“We’d just like to have it back, we would be happy to have it back however.”
The quadrangular iron bell is coated with bronze and had been encased behind a locked metal cage within a niche purposely built into the church’s wall.
This had been broken into and the priceless item removed.
The parish church is on an early Christian site, dedicated to Coeddi, bishop of Iona.
It is believed to have been founded from the Hebridean island as a daughter monastery, around 700.
Any information which may lead to the bell’s return is being asked by Police Scotland to call 101 quoting reference number CR/23634/17.
A Celtic handbell from the seventh century which holds “significant” sentimental value has been stolen from a church.