The head of the Roman Catholic Church joined the site earlier this month and already had over 660,000 followers before posting his first message.
"Dear friends, I am pleased to get in touch with you through Twitter," he said.
"Thank you for your generous response. I bless all of you from my heart."
Last year, the Pope tweeted from a Vatican account to launch the Holy See news information portal.
The Vatican said that he will "tweet what he wants to tweet" from @pontifex, although he is expected to sign off rather than write the messages.
"We are going to get a spiritual message," Greg Burke, senior media advisor to the Vatican, said in a statement.
"The Pope is not going to be walking around with a Blackberry or an iPad and no-one is going to be putting words into the Pope's mouth."