In her announcement, Williams said that she will soon return to the Australian Open, but will first focus on her daughter.
Six-time Australian Open victor Djokovic still remains highly doubtful for the Australian Open but will be travelling to Australia to compete in the Tie Break Tens at the Margaret Court Arena at Melbourne Park on January 10.
The 36-year-old American last week played her first match since giving birth in September.
There are also doubts over the fitness of Spanish world number one Rafael Nadal and Switzerland's Stan Wawrinka, who won the title in 2014.
Williams previous year beat older sister Venus in the final.
Jose Mourinho bites back at Antonio Conte with match-fixing taunt
Reports emerged on Thursday evening claiming there were fears inside Old Trafford that Mourinho could resign after two seasons. You have to accept the decision. "He's experienced, won a lot, but he needs to continue what he has done in the past".
After Andy Murray and Kei Nishikori, Serena is the third big name to pull out of the season opening Grand Slam, starting later this month.
Serena will sit one out, but is promising to return in future. On January 4, the tennis champ shared her decision to withdraw from the 2018 Australian Open, and offered a heartfelt explanation as to why.
Tournament director Craig Tiley called Williams's efforts to try and be ready for a title defence at the Australian Open "Herculean" and said she transcended the sport.
"I've been in constant contact with Serena and her team and know this is why she has pushed it and pushed it until the eleventh hour to make her final decision". At that time, she and Ohanian were still not married.
Romanian Simona Halep, the current world No.1, and Dane Caroline Wozniacki are jostling for women's top seeding status in Melbourne.
Also in the mix will be No. 2-ranked Garbine Muguruza, last year's Wimbledon victor, U.S. Open champion Sloane Stevens and Venus Williams, who will be aiming to win her eighth major singles title at the age of 37.