Chen announced her decision via a taped message on the show Tuesday, saying she needed to spend more time at home with her husband and their son.
No less than 12 women have come forward to accuse Moonves, the former CEO of CBS, of various forms of sexual harassment and assault, including forced oral sex and retribution when his advances were declined.
CBS waited until the final minutes of Tuesday's hour-long episode to address the elephant in the room.
CBS later thanked Chen for her time on The Talk in a statement.
The day after the ousting news broke, Chen announced that she "was taking a few days off from The Talk to be with my family" but "will be back soon". Most important, I want to thank you, the viewers, for allowing me into your home every day.
'To everyone behind the scenes, I send you my love and I will miss you all very, very much, ' said Chen.
After Chen's comments, Talk creator Sara Gilbert - who has co-hosted the show with Chen since its inception in 2009 - thanked Chen for her time on the program.
That show of support has many thinking Chen will finish out her Big Brother contract (the summertime show wraps next week) and then exit CBS for good. All of us here have tremendous appreciation for the dedication and passion she brought to the show every day and for her generous role as an ambassador for CBS Daytime. "We love you, Julie".
The most recent allegations against Moonves, which follow-up on original allegations made in late July, were published in The New Yorker, and reportedly range from the mid-1980s into the early 2000s. On the talkshow, the hosts regularly chat about their personal lives.
Julie Chen did return to live TV last week to helm the double eviction episode of Big Brother.
'I will always cherish the memories we shared, ' said Chen.
With Les battling these misconduct allegations, reports claimed that Julie's priorities changed, with "clearing her husband's name" and tending to her son, 8-year-old Charlie Moonves, suddenly becoming her main focus. I've spent eveyr day with you both, and I will always treasure our friendship, the great parenting advice from both of you, and the memories and laughs and private jokes we shared. "I fully support my husband and stand by him".
She publicly supported Moonves after a first round of accusations last month, saying he was a "decent and moral human being".
A second New Yorker story by Ronan Farrow came out on September 9.
Moonves had denied the allegations.