"Should abortion be punished?" Matthews said.
"The answer is that there has to be some form of punishment," Trump responded. "There has to be some form."
The comments were particularly notable because they appeared to backfire among the very voters Trump was trying to court: those opposed to abortion.
Anti-abortion advocates have a long history of supporting punishments for abortion providers, but not patients.
The comments were quickly seized on by his two rivals for the GOP nomination, Senator Ted Cruz of Texas and Governor John Kasich, to suggest that Trump, who in the past has said that he supports abortion rights, misspoke because he is not a true opponent of abortion.
"Once again Donald Trump has demonstrated that he hasn't seriously thought through the issues, and he'll say anything just to get attention," Cruz said.
"On the important issue of the sanctity of life, what's far too often neglected is that being pro-life is not simply about the unborn child; it's also about the mother - and creating a culture that respects her and embraces life."
The Susan B. Anthony List, a prominent anti-abortion group, also released a statement stressing women should not be punished for undergoing abortions.
"We have never advocated, in any context, for the punishment of women who undergo abortion," said Marjorie Dannenfelser, the group's president.
"Let us be clear: Punishment is solely for the abortionist who profits off the destruction of one life and the grave wounding of another."
Democratic front-runner Hillary Clinton also responded immediately via social media.
"Just when you thought it couldn't get worse. Horrific and telling," Clinton wrote on Twitter.
Women's groups were quick to weigh in as well, including Planned Parenthood Action and Emily's List, both of which called Trump dangerous and blasted his comments.
"The last person women need to police their health-care decisions is someone who sees them not as people, but as 'fat pigs,' 'bimbos' and 'disgusting animals'," said Emily's List communications director Marcy Stech.
"Republicans are about to nominate a truly dangerous man to lead their fight to restrict women's access to abortion."
Dawn Laguens, executive vice-president of the Planned Parenthood Action Fund, said: "Donald Trump is flat-out dangerous. Women's lives are not disposable.
Trump retreated from his comments within hours, clarifying that he believes decisions about punishments should be left to the states to decide.
He further clarified that he does not think such punishments should focus on the women, a reversal from his earlier comments.