Five of the court's nine justices questioned the constitutionality of the 1996 law Wednesday during a second day of arguments on laws related to gay marriage.
DOMA denies married same-sex couples access to federal benefits like Social Security by defining marriage as between one man and one woman.
The court heard about two hours of arguments on the law a day after lawyers presented cases for and against California's gay marriage ban.
While Supreme Court justices appeared hesitant to rule on Proposition 8, several justices spoke out strongly against DOMA during today's arguments.
Justice Ruth Bader Ginsburg said it effectively creates a two-tiered system of marriage.
“There are two kinds of marriage,” The New York Times quoted her as saying. “Full marriage and the skim-milk marriage.”
Justice Anthony Kennedy, a potential swing vote, warned that DOMA may infringe upon the traditional role of states in defining marriage.
SCOTUSblog, a blog that tracks the Supreme Court, gives DOMA an 80 percent chance of being overturned based off today's hearing.
Rulings on the gay marriage cases aren't expected until June.