‘Betty Brown’s Eyes’ was a tribute to Betty Brown, from Garnethill, Glasgow, a former chair of her local community council.
The art work, at an area known as the Viewpoint near Hill Street, was created six months ago with help from Glasgow School of Art.
But locals have been left saddened and shocked after vandals spray painted a massive graffiti tag right across the poignant image.
Someone has also sprayed “f**k art” next to the mural.
Garnethill MSP Sandra White called for those who “desecrated the memory of one of the city’s hardest working women” to own up.
It is feared that the cost of fixing the mural could total £1,500.
Ms White said: “I knew wee Betty.
“She was a fantastic person who worked tirelessly for Garnethill - she was Mrs Garnethill.
“I wonder if those who have carried out this terrible vandalism know of Betty, and what she did for the area?
“They should be ashamed of themselves. I would ask them to own up and come forward.”
Mrs Brown died in 2006 aged 76.
She spearheaded a number of campaigns for a park, a play area, a community shop and the multi-ethnic hall.
She also campaigned on road safety for children, organised litter clear-ups and galvanised locals into fun days and social activities.
Garnethill Park, once a rubbish tip, is one of her lasting legacies.
A plaque in her memory sits within the park as well as at the nearby multi-cultural centre.
A spokeswoman for Police Scotland said: “We have received reports of a vandalism at Hill Street in Garnethill.
“Enquiries are ongoing.”
Anyone with any information can contact officers on 101.