The couple had previously pledged to give away at least half their assets, so Tuesday's announcement that they're giving away nearly all their wealth has stunned just about everybody.
Zuckerberg and Chan are now the proud parents of a little girl named Max.
The couple posted a photo on Facebook, and with it a letter to their daughter: "Max, we love you and feel a great responsibility to leave the world a better place for you and all children."
"The only way we reach our full human potential is if we're unable to unlock the gifts of every person around the world," Zuckerberg said.
The Zuckerberg's plan to give away 99 percent of their Facebook shares over the course of their lives dwarfs their previous $1.6 billion in pledges to charitable causes including the $75 million to San Francisco General Hospital, and $15 million to San Francisco's private school start-up, AltSchool.
Alt School founder and CEO Max Ventilla thinks $45 billion "is really an enormous amount of money to fuel initiatives that wouldn't otherwise started."
The Zuckerbergs are certainly breaking the stereotype of tech leaders, who've gained a reputation for holding back on charitable giving. Daniel Lurie, founder and CEO of the nonprofit Tipping Point Community, hopes this is the start of a trend.
"We have great role models here in the Bay Area, Marc Benioff, Mark Zuckerberg and Priscilla Chan. We have others who can do the same thing and we hope they can step up as well," Lurie said.
It is a call to action that was set in motion by the birth of a child.