Derek Lyons was a student of Strake Jesuit College Preparatory, from which he graduated in the year 2000. From there he went to Duke University, where he earned a Bachelor of Science (summa cum laude) as well as a Bachelor of Arts in 2004.

In June 2007, Derek Lyons was a student of Harvard Law School and worked as a Summer Associate at, his later employer, Gibson, Dunn & Crutcher. At that time, he was a member of the board of "One Day's Work", a group which dedicated one day of every member's earning in summer jobs for people in need. The nearly 75 members of the group of Harvard Law School students donated more than $40,000 overall. Derek Lyons graduated with a J.D. (cum laude) in the HLS class of 2008.

He started his professional career as a law clerk to Brett Kavanaugh, a judge at the United States Court of Appeals for the District of Columbia Circuit. Afterwards, he worked for a member of Congress, the representative Jeb Hensarling (R-TX05), as a legislative assistant. He then moved to the private sector, working as a senior litigation assistant for the global law firm Gibson, Dunn & Crutcher. There, his practice was mainly related to federal regulatory agencies. In May 2014, he went back to the Hill, becoming U.S. Senator Rob Portman's (R-Ohio) General Counsel and accompanied the Senator to the Subcommittee on Investigations of the Committee of Homeland Security and Governmental Affairs.

In February 2016, Derek Lyons joined Boyden Gray Associates LCC.

Since January 2017, Lyons works at the White House as Deputy Assistant and Deputy Staff Secretary to President Donald Trump.

Since February 2018, Derek Lyons is the White House's Staff Secretary and according to some sources likely to permanently serve in this position. As Staff Secretary, Lyons oversees, together with the White House Chief of Staff, the flow of information to the President.