The team – made up of English, Indian and Sri Lankan clergy – comfortably beat a team of armed forces chaplains by 81 runs.
It was the first of a five-game series that will culminate in a match against the Church of England.
The team was not so successful in the second game, losing out to St Peter's Cricket Club, Brighton.
Next up is an Authors XI before a team put together by the Queen.
The Church of England team has one practice game on Wednesday before the big match and its captain, Rev Jez Barnes from St Stephen's in Twickenham, is quietly confident.
He said: 'The Vatican team have been playing together for a year; we're more of a scratch side.
'We've had to put our team together on the hoof, but we've got a great bunch of guys on our team.'
The game, which has the support of the Archbishop of Canterbury and Pope Francis, was organised to raise money for a joint Catholic and Anglican campaign against modern-day slavery and human trafficking.
It takes place on Friday 19th September at Kent County Cricket Club in Canterbury.
Hear more from Rev Jez Barnes on Premier's Inspirational Breakfast show: