The Grey's Anatomy star broke the news Tuesday, telling Us Weekly in a statement that she and Lanfer were "delighted to announce our pregnancy."
"We can't wait to introduce Micah to his little brother or sister," Drew added.
The 33-year-old actress who is due in December, married Lanfer in June 2002. The couple welcomed their first child, Micah, in January 2012.
"I got great advice about nausea from Ellen Pompeo because I am still dealing with nausea, which is no fun," she said of her co-star during her first pregnancy. "She's a wealth of information: She's done all the research and looked into every possible way of doing things."
Drew is best known for playing doctor April Kepner in the ABC medical drama and for voicing Stacy Rowe for MTV's Daria. She's also had guest roles in TV's Supernatural, Miami Medical, Glee and others.