Murphy graduated from Harvard College and Radcliffe College magna cum laude in 1984, and from Harvard Law School cum laude in 1987. Murphy clerked for a judge in the United States Court of Appeals for the Second Circuit (1987–1989), and later worked as a lawyer for the Justice Department (1989–1990). She has also taught law at Temple University, worked for NARAL Pro-Choice America, and is now a member of a private law firm. She was appointed by Governor Ed Rendell to the Pennsylvania Commission for Women in 2003, and is a trustee of the Women's Law Project.
Lois Murphy is married to lawyer Benjamin Eisner, whom she met at Harvard. They have two daughters, Emily and Lily. Emily Eisner is a graduate of Dartmouth College class of 2014. Lily Eisner is currently attending Dartmouth College.
In 2002 she ran Pennsylvania Governor Ed Rendell's campaign in Montgomery County, Pennsylvania.
In 2004, she ran for Congress against Republican Jim Gerlach. She lost by 2%, the closest margin for an incumbent re-elected that year.
In 2006, in a rematch of the 2004 race, she lost to Gerlach by 1.2%.
2004 - United States House of Representatives
Lois Murphy - 153,977 - 49.0%
Jim Gerlach - 160,348 - 51.0%
2006 - United States House of Representatives
Lois Murphy - 115,806 - 49.4%
Jim Gerlach - 118,807 - 50.6%
In 2006, Murphy won the Democratic Party primary over Mike Leibowitz, a real estate executive, with 73 percent of the vote. She again faced Gerlach in the general election. Gerlach was at that time considered one of the most vulnerable congressmen in 2006, in November.
As of September 30, 2006, Gerlach had raised $2.9 million compared to Murphy's $2.8 million, and had $1.2 million cash on hand versus Murphy's $900,000. The National Republican Congressional Committee spent $1.6 million in support of Gerlach.
In unofficial results as of November 8, 2006, Murphy lost by 3,001 votes (about 1.2%). See Pennsylvania 6th Congressional District election, 2006 for details.
On November 3, 2009, she was elected to the Montgomery County Court of Common Pleas, the only Democrat to win election to the court.