"Dear friends, I thank you from my heart and ask you to continue to pray for me," the pope tweeted from the @Pontifex account, which was previously used by Benedict XVI.
The 76-year-old Pope Francis's first tweet had over 13,000 retweets within the first hours of posting.
After Pope Benedict officially resigned, all tweets were erased from the feed and the @Pontifex account holder's name was changed to "Sede Vacante" to signify the papacy was vacant.
Shortly after Pope Francis was elected, the Vatican used the papal Twitter account to tweet "Habemus Papam Franciscum" (We have a pope named Francis).
The tweet came three months after the Vatican launched the first ever personal Twitter account for the Pope, with tweets going out in nine languages.
The Pope's English account has nearly 1.6 million followers.
Cardinal Jorge Mario Bergoglio of Buenos Aires was elected the 266th pope by the conclave of cardinals March 13, becoming the first Latin American to lead the Catholic Church.
The inauguration of the new leader of the world's 1.2 billion Catholics will be held March 19.