Gertner began her legal career in 1971 as a law clerk for Judge Luther Swygert of the United States Court of Appeals for the Seventh Circuit.

During this period, Gertner was notable for being a supporter of liberalism and feminist ideals, wearing bright red clothes in court, carrying her legal briefs in shopping bags and keeping files on lawyers and judges she felt to be sexist.

The case interpreted new admissibility standards for expert testimony set forth by the Supreme Court in Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993) and Kumho Tire Co. v. Carmichael, 526 U.S. 137 (1999).

On July 26, 2007, she ordered the federal government to pay a record $101.7 million for withholding evidence that could have exculpated four men wrongfully convicted of murder.

[6] The men had been falsely accused by mob hitman Joseph "The Animal" Barboza, with the help of corrupt FBI agent H. Paul Rico.

[9] Sean Hannity, Rush Limbaugh, Alan Dershowitz and others have asserted that Robert Mueller was responsible for the improper imprisonment of four men when he was a federal prosecutor in Boston during the 1980s.

In an opinion piece entitled "Smearing Robert Mueller", Gertner, who presided over the matter, wrote "[t]he record simply doesn't support these assertions".

[13] In October 2015, Gertner became the subject of media attention in the Boston area when an escaped cockatoo did considerable damage to her Brookline residence, a historic Victorian home which also happened to be the birthplace of Robert F. Kennedy.