Mrs Obama's account, @michelleobama, will be managed by aides on the Obama campaign, with any tweets from the first lady herself to be signed "-mo."
Within a few hours, the first lady was closing in on 100,000 followers.
The president's account, @barackobama, is also managed by campaign officials, separate from the @whitehouse account.
Mrs Obama's arrival on the social media site sees her following in the footsteps of hundreds of politicians, candidates and campaign staff ahead of November's election.
She was given a boost when her husband's account - but not her husband himself - told the president's 11 million followers that the first lady had joined Twitter.
"It's not every day we get to welcome the First Lady of the United States to Twitter - happy to have you, @MichelleObama!"
Mrs Obama's first personal tweet included thanks for the "warm welcome".
"Look forward to staying in touch with you here."