The Most Rev Vincent Nichols, Archbishop of Westminster and leader of Catholics in England and Wales, called on "people of faith" to pray for the 85-year-old pontiff, saying that his announcement had shown "great courage."
"Pope Benedict's announcement today has shocked and surprised everyone," he said.
"Yet, on reflection, I am sure that many will recognise it to be a decision of great courage and characteristic clarity of mind and action."
Cardinal Cormac Murphy-O'Connor, who retired as Archbishop of Westminster in 2009, said: "My reaction was one of surprise and then gratitude for his service and leadership of the Church over the past seven years in troubled times.
"He has been a great teacher, thinking particularly of his visit to Britain and the example he gave of being a Good Shepherd and a good pastor."
"My first thought when I heard the news that he was resigning, my instinct was that it is because of his health and his frailty and he feels it is an incredibly responsible task to be the chief shepherd of the Church on earth," he said.
Prime Minister David Cameron, who met the Pontiff in Archbishop's House, near Westminster Cathedral in London on his visit to Britain in 2010, said: "He has worked tirelessly to strengthen Britain's relations with the Holy See.
"His visit to Britain in 2010 is remembered with great respect and affection. He will be missed as a spiritual leader to millions."
Labour leader Ed Miliband said Pope Benedict had made a "brave" decision.
"Many people will remember his historic visit to the UK in 2010 - which was a very special moment for many, especially Catholics, across the country," he said.
"His decision to stand down is a brave one and we know he will not have reached it lightly.
"The choice of a successor is clearly an important one for the Catholic Church.
"Our thoughts are with those who must make such a critical decision on behalf of millions around the world."
German Chancellor Angela Merkel said she had the "very highest respect" for his decision to step down.
"As chancellor, I thank Benedict XVI for his work and wish him from the bottom of my heart all the best for the coming years," she said.
Merkel, who is a Protestant, praised Benedict for his efforts to promote dialogue with other Christian denominations and religions. She said that he "reached out his hand to Jews as well as Muslims."
New York Cardinal Timothy Dolan, tipped as an long-shot for the pope's replacement, said he was as startled as the rest of the world.
He said he felt a special bond with the pope because he was the one that appointed him archbishop of New York.