The 85-year-old religious leader, who was elected Pope in 2005, is to retire within the next two weeks, making him the first head of the Catholic Church to step down in almost 600 years.
Stars including actress Mia Farrow and singers Boy George and Ricky Martin took to Twitter.com to weigh in on the news, but a handful of comics took the chance to poke a little fun at the Pope.
Gervais asked, ""Being 'The Pope' means you are married to God. So, is this like a divorce?"" and Pegg quipped, ""The Pope has resigned! Surely he can only be fired? God?""
The Star Trek actor then joked to his fans, ""I think he got headhunted by Buddha... Do you think there was a moment when the Pope was giving mass on the Vatican balcony and thought, 'I'm too old for this s**t'?""
Walliams tweeted, ""I have just been asked to be the new Pope. My agent is trying to do a deal with the Vatican as I don't like to work on Sundays.""
Actor/comedian Kevin James added, ""From now on, when someone snarks you with 'Is the Pope Catholic?' you can say 'He's not even the Pope anymore'..."" and funnyman Patton Oswalt suggested Vatican bosses stage a reality TV talent contest to find a replacement: ""Top Pope. Reality competition. Do it, Vatican.""
Farrow told followers she is hoping for an open-minded replacement, writing, ""Hoping for a more progressive successor - imagine a pope more like Arch Desmond Tutu,"" and Boy George agreed, adding, ""A new radical Pope perhaps? Let's pray!""