The 32 year old, who has played Sonia Fowler in the BBC One soap since 1993, announced that she is expecting the new addition to her family in the summer.
Although Natalie is already a mother-of-one, it will be her first child with current partner Marc Humphreys.
Taking to her Twitter account, Natalie told her 300k followers; 'Evening all... Time to let everybody know that @cameramarc and I are having a baby in the summer. The three musketeers become four.'
Evening all... Time to let everybody know that @cameramarc and I are having a baby in the summer. The three musketeers become four.— Natalie Cassidy (@Nat_Cassidy) February 12, 2016
The Sun has reported that the pair are expecting a son this time around, but this has been disputed by the couple.
The twice-British-Soap-Award winner already has a five-year-old daughter, Eliza Beatrice Cottrell, from a previous relationship.
In March 2010 Natalie announced she was pregnant with her first child with then-boyfriend Adam Cottrell, but the pair split after Adam was charged with two offences of assault and criminal damage against Natalie.
Speaking about the relationship with her former fiancée, the Celebrity Big Brother star said; 'Adam's behaviour was unacceptable, but so was mine. I can see that now.
'I often lashed out physically at him when arguments weren't going my way. I would hit him or slap him out of frustration and anger.'
Natalie with on-screen husband Martin Fowler
The Strictly Come Dancing contestant met her current partner Marc on the set of EastEnders, where he is a freelance cameraman.
They got engaged in October 2015 after celebrating their first anniversary together.
Natalie has also released two singles as a solo artist but after receiving bad reviews she has no plans to make any more music.
It has not been confirmed whether Natalie's pregnancy will mark her departure from EastEnders.
Natalie as Sonia, 2005
Natalie has previously said she wouldn't want her children to become actors as it is important to have some anonymity in life; 'As soap stars we're statistically the most famous people in Britain.'
'Bigger than Brad Pitt because you might watch one film a month but we're there four times a week. I don't think I've ever been on holiday and not been recognised.'