His first tweet: "Dear friends, I am pleased to get in touch with you through Twitter. Thank you for your generous response. I bless all of you from my heart."
The pope's handle is @Pontifex, the Italian news agency ANSA reported.
Monsignor Paul Tighe, secretary of the Pontifical Council for Social Communications, called the event "an extraordinary moment," Vatican Radio reported.
The pope's post generated more than 2,000 re-tweets in less than two minutes, Tighe said.
Vatican Radio said the number of Pope Benedict's followers topped 1 million.
Now that he's using the microblog, Vatican officials said Pope Benedict spent Wednesday afternoon responding to selected questions from those submitted to #askpontifex.