Mell is the daughter of long-time Alderman Richard Mell. Her sister, former Illinois First Lady Patti, is married to former Governor Rod Blagojevich.
Mell was educated in Chicago, at St John Berchman’s Elementary School and St Scholastica High School. She then attended Cornell College with a dual major in political science and history, before earning a culinary arts degree from California Culinary Academy.
Mell returned to Chicago in 2000 and began working at Christy Webber Landscape, Chicago’s largest landscaping company owned by prominent lesbian Christy Webber.
Mell was arrested in 2004 while protesting her inability to get a same-sex marriage license from the Cook County clerk's office.
The 40th district, located on Chicago's northwest side, was represented by Rep. Rich Bradley prior to 2008. Bradley decided not to seek re-election in 2008 after Mell announced that she was running, choosing instead to challenge Sen. Iris Martinez for a seat in the Illinois Senate. Mell's campaign had the support of the Gay & Lesbian Victory Fund. She won 75% of the vote in the general election of November 4, 2008; her opponents, Republican Christine Nere-Foss and Green Party candidate Heather Benno, garnered 15% and 10% respectively.
On January 14, 2009, in one of her first votes in the Illinois House of Representatives, Mell cast the lone vote opposed to impeaching her brother-in-law, then-Governor Rod Blagojevich. This was the second time the House had voted to impeach Blagojevich, and the tally was 117–1.
In November 2008, Mell expressed interest in running in the special election to replace Rahm Emanuel, who would be resigning from the U.S. House of Representatives to serve as President Obama's White House Chief of Staff. Several weeks later, she withdrew from the race.
In July 2013, Alderman Richard Mell, Deb Mell's father, retired from the city council after nearly 40 years. Mayor Rahm Emanuel was charged with appointing his successor and settled on Deb Mell. The appointment was announced on July 24 and confirmed by the city council later that day.
Mell is openly lesbian. She was married to Christin Baker from 2011 to 2014. She was one of four openly LGBT members of the Illinois General Assembly, along with Reps. Greg Harris and Kelly Cassidy, both Democrats from Chicago, and Sam Yingling a Democrat from Round Lake Beach, Illinois, in suburban Chicago.
Mell served on former Mayor Richard M. Daley's Advisory Council for Human Relations and is active in numerous LGBT activist groups. She has received a National Organization for Women award for her activism, as well as the Howard Brown Cornerstone Award for community excellence.