In a tweet, Musk said he would remain in charge of design and technology at Twitter, with Yaccarino focusing primarily on business operations and turning Twitter into an "everything app" called X.
Musk on Thursday teased Yaccarino's hiring saying in a tweet that he had hired a woman to replace him as boss of Twitter and its newly named X Corporation parent, but without revealing the name.
Yaccarino's departure from the company that owns NBC, Universal and Telemundo - where she has been since 2011 - came a few weeks after she interviewed Musk at a marketing conference in Miami.
Asked by Yaccarino at the time how it's been going since the acquisition, Musk replied: "It's going well...It's entertaining....It's a train wreck sometimes."
Twitter is struggling to find its footing after Musk's controversial takeover that saw him fire thousands of staff and welcome back far-right and controversial figures on the platform, spooking away its highest paying advertisers.
Yaccarino is one of the advertising industry's most respected executives, but will face an uphill battle trying to attract major companies to come back to the platform.
Musk's history with the letter X goes back to 1999 when he helped created X.com, an online bank that was bought and later morphed into PayPal.
He has also longed to create a so-called everything app that would be modeled on China's WeChat which functions as Twitter-like social media as well as offering messaging and mobile payments.
Musk has fully owned Twitter since late October and has repeatedly courted controversy as CEO, sacking most of its staff, readmitting far-right figures to the platform, suspending journalists and charging for previously free services.
With Yaccarino's hiring, he is belatedly fulfilling the promise he made to honor the results of a Twitter poll he posted in December.
In that unscientific survey, a total of 57.5 percent of more than 17 million accounts voted for him to step down.
Wall Street had grown frustrated that Twitter was luring Musk away from his other businesses, and share prices in Tesla rose on news he had found a CEO.