A total of 56 persons have served as United States District Judges in the Eastern District of Louisiana during its 200-year history. For the first 166 years of those two centuries, all of the court's 30 judges were white men. During the past 45 years, however, the makeup of the court has changed.

The race barrier was broken in 1978, when President Jimmy Carter appointed Judge Robert F. Collins to the district bench. He was followed in 1994 by Judge Okla Jones II, then City Attorney of New Orleans, who was appointed by President William J. Clinton, and whose untimely death only two years later cut short a promising judicial career. The next African American district judge, Judge Ivan L.R. Lemelle, was appointed by President Clinton in 1998, and had served previously as the court's first African American magistrate judge. Thereafter, Judge Nannette Jolivette Brown, who, like Judge Jones, was the City Attorney of New Orleans at the time of her appointment, was appointed in 2011 as the court’s first African American woman district judge by President Barack Obama, and began serving as the court's first African American chief judge in 2018.

The gender barrier was overcome in 1979, when President Carter appointed Judge Veronica DiCarlo Wicker to a district court judgeship. Judge Wicker had also been the court's first woman magistrate judge. Judge Wicker, who presided until her death in 1994, has been followed by  eight distinguished women: Judge Edith Brown Clement (1991-2001), who was appointed by President George H.W. Bush and became the court's first woman chief judge before her elevation by President George W. Bush to the United States Court of Appeals for the Fifth Circuit, where she currently serves; Judge Helen Ginger Berrigan (1994-present), a practicing attorney who was appointed by President Clinton, and served a term as the court's chief judge, Judge Sarah S. Vance (1994-present), a practicing attorney who was appointed by President Clinton, and who also served a term as the court's chief judge; Judge Mary Ann Vial Lemmon (1996-present), who previously served as a Louisiana state court trial judge and was also appointed by President Clinton as the first judge from the River Parishes; Judge Nannette Jolivette Brown (2011-present), currently serving as Chief Judge; Judge Jane Triche Milazzo (2011-present), a former Louisiana state court trial judge, who was appointed by President Obama; Judge Susie Morgan (2012-present), a practicing attorney, who was appointed by President Obama; and Judge Wendy B. Vitter (2019-present), a practicing attorney, who was appointed by President Donald Trump.

The court's Article I judges, consisting of magistrate judges, appointed by the Article III judges of the district court, and bankruptcy judges, appointed by the Article III judges of the Court of Appeals, have also reflected the growing diversity of the Eastern District. Asian-American magistrate judge, Harry Lee, African American magistrate judges, Louis Moore, Jr. Karen Wells Roby, Dana M. Douglas, and women magistrate judges, Eileen Gleason Shaver, Michaelle Pitard Wynne, Alma Chasez, Sally Shushan, Janis van Meerveld, and Donna Phillips Currault have also served on the Eastern District court. Additionally, in 2005, Judge Elizabeth Magner became the district's first female United States Bankruptcy Judge, and in 2019, Judge Meredith S. Grabill was sworn in as the district’s second female United States Bankruptcy Judge.