Streisand said she was motivated to contribute to women's heart health because she "can't stand inequality, whether it's about civil rights, gay rights or gender discrimination."
Heart disease kills more women each year than all cancers combined, but most of the research on the disease for the past five decades has been conducted on men.
"Even in scientific research, women are still treated as second-class citizens," Streisand said, "and to me, that's just unacceptable."
So she raised her voice and opened her wallet, and invited her friends to do the same.
"It's kind of a selfish thing, because it's actually very fulfilling, to do something like that that's larger than me or my career," she said, acknowledging that her fellow donors must feel the same way.
"Think about all the good that we'll do, all the good that will come of it, because of your extraordinary generosity," she said.
Clinton, who was introduced by journalist Lisa Ling and welcomed with a standing ovation, saluted Streisand for her commitment to women's health.
"I never thought anybody could care a lot about more things than I care a lot about. She makes me look like a heartless dumb piker," he said. "Unless your heart has been taken out of your body, you need to care about this."
Clinton said that the issue of heart health and equitable research goes beyond politics.
"Our country has always believed in being not only a laboratory of democracy but a laboratory of science and advancement, and you can't do that with a straight face and leave women out," he said.
Singer Josh Groban performed before Streisand took the stage. Streisand sang four songs, including the Oscar- and Grammy-winning "Evergreen," which she dedicated to Clinton. He told her in 1992 that it was his favorite song of hers, and she sang it at his inauguration.
Streisand and Groban performed a duet of "Smile," and Streisand closed the evening with a special version of "Here's to Life," with new lyrics by Alan and Marilyn Bergman, who were also among the guests Thursday.
"A woman's heart beats well tonight," Streisand sang. "Because of you, a woman's future's looking bright. And it gets even brighter with each check you write, so thanks with all my heart."