She first came to prominence in 1991, covering the William Kennedy Smith trial for CNN. She was noticed by the network's programming executives and was given a co-anchor spot alongside political analyst Roger Cossack on the legal affairs news show Burden of Proof. She also hosted the primetime program The Point with Greta Van Susteren, which was the second highest rated program on CNN.

In 2002, the Fox News Channel snagged her in a highly-publicized contract bidding war.

Since that time, she has hosted the current affairs show On the Record with Greta Van Susteren and has become one of the network's more popular personalities, on par with Bill O'Reilly and Hannity & Colmes. Van Susteren tends to take a neutral stance and allows her regular guest panelists to slug it out. She tends to ask detailed, probing questions, in the manner of a well-trained attorney trying to get the facts out.

Van Susteren graduated from Xavier High School in Appleton, Wisconsin in 1972, and earned her bachelor's degree from the University of Wisconsin in 1976. Van Susteren also studied law at Georgetown University Law School, earning both a Juris Doctor and a Master of Laws (1979, 1982). She is of Irish ancestry on her mother's side as well as 1/4 Dutch, 1/8th French and 1/8th German on her father's. Her father Urban Van Susteren was an old friend, fellow law student, and later campaign strategist for Joe McCarthy's successful 1946 U.S. Senate campaign where he defeated two-term incumbent Robert LaFollette, Jr., in a three-candidate race.

Lise Van Susteren, sister of Greta, was formerly a candidate for the Democratic nomination for U.S. Senate from the state of Maryland. Lise is a forensic psychiatrist from Bethesda, Maryland. Greta is also a practicing Scientologist.