The news was broken by 35-year-old Chelsea herself on Twitter.
"Next summer, Charlotte is going to be a big sister! Feeling very blessed and grateful this holiday season," she said.
The announcement accompanied a picture of her first child 1-year-old Charlotte, looking at a book that says "Big Sisters are the Best".
The birth would come in the middle of the intense battle for the US presidency and Chelsea's mother - the Democratic frontrunner - is widely expected by next summer to be her party's nominee ahead of the November election.
More From This Section
"Being Charlotte's parents has been the most joyous, meaningful and loving experience of our lives and we are very excited about growing our family in the new year," she wrote.
Both Bill Clinton and wife Hillary took to Twitter to express their excitement on the news about becoming second- time grandparents soon.
"Christmas comes early! Hillary Clinton and I are thrilled for Chelsea, Marc and Charlotte's growing family in 2016!" Bill Clinton tweeted.
Chelsea Clinton, who is vice chair of the New York-based Clinton Foundation launched in 2001 by her father, has also wrote a children's book published in September called 'It's Your World: Get Informed, Get Inspired & Get Going!' that offers young people a guide to making a difference in the world.