The priest at St Andrew's RC Church in Livingston said anti-Catholic messages had been painted all over the building.
The vandalism happened between 19:00 on Saturday and 09:00 on Sunday.
Police have urged anyone who may have seen anything suspicious in the area, or anyone with information, to come forward.
In April 2014, St Andrew's Roman Catholic Church in Craigshill became the latest building in Livingston to be granted listed status.
Designed in 1968 and completed in 1970, St Andrew's was the first Catholic Church to be built in Livingston after it was founded in 1962.
Father Jeremy Bath, parish priest of St Andrew's, said: "Craigshill is a great area where people live together in harmony so for this to happen is shocking, saddening and very disappointing.
"I've been here for seven years and nothing like this has happened before. Hence the disappointment. It's perhaps a reminder that there is still a strain of anti-Catholicism in Scottish society that we have to be aware of.
"We had a funeral today. How sad that mourners had to arrive at a church covered in anti-Catholic graffiti. Hopefully we can get things cleaned up very soon, certainly in time for our First Holy Communions this weekend.
"I'd like to thank Police Scotland, West Lothian Council and the local community for being so supportive at this difficult time."
A Police Scotland spokesman said: "Police in West Lothian are investigating following sectarian vandalism to a church in Livingston.
"The incident happened sometime between 19:00 on Saturday 23 May and 09:00 on Sunday 24 May at the St Andrews Roman Catholic Church in Victoria Street, Craigshill.
"Inquiries are ongoing to trace those responsible and anyone who remembers seeing anything suspicious in the area, or who has information that can assist police with their investigation is asked to come forward immediately."
A West Lothian Council spokesman said: "We were made aware of this incident at St Andrew's RC Church in Craigshill on Sunday and our street cleansing team have been in attendance."

Cafodd yr heddlu a pharafeddygon eu galw yn dilyn adroddiadau o ffrwgwd ym Mynwent y Gorllewin yn Nhrelái am 14:45 ddydd Llun.
Fe wnaeth tri dyn ddioddef anafiadau yn ystod y digwyddiad rhwng unigolion oedd yn "adnabod ei gilydd" meddai Heddlu De Cymru.
Nid yw'r anafiadau'n rhai sy'n golygu fod eu bywydau mewn perygl ac nid yw'r heddlu wedi arestio unrhyw un.
Dywedodd Cyngor Caerdydd fod staff yr awdurdod yn cynorthwyo'r heddlu ond nid oedd y fynwent wedi ei difrodi.
Cafodd dau ddyn eu cludo i Ysbyty Athrofaol Cymru yn y brifddinas, ac fe gafodd dyn arall ei gludo i Ysbyty Frenhinol Morgannwg.
Police are investigating an incident of sectarian graffiti sprayed on a church in West Lothian over the weekend.
[NEXT_CONCEPT]
Mae tri o bobl wedi eu hanafu yn dilyn digwyddiad mewn mynwent yng Nghaerdydd.