- Born on September 14, 1978, in Jacksonville, Florida, the son of Karen (née Rogers) and Ronald DeSantis. He is of Italian descent. His family moved to Orlando, Florida, before relocating to Dunedin, Florida when he was six years old.
- In 1991, he was a member of the Little League team from Dunedin National that made it to the Little League World Series. He was captain of Yale's varsity baseball team (an outfielder); as a senior in 2001, he had the team's best batting average at .336.
- DeSantis attended Yale University. He and joined the Delta Kappa Epsilon fraternity. He graduated from Yale in 2001 with a B.A. magna cum laude in history.
- He then spent a year as a history teacher at the Darlington School.
- DeSantis then attended Harvard Law School, graduating in 2005 with a Juris Doctor cum laude.
- DeSantis received his Reserve Naval officer's commission and assignment to the Judge Advocate General's Corps (JAG) in 2004 at the US Naval Reserve Center in Dallas Texas, while still a student at Harvard Law School.
- He completed Naval Justice School in 2005. Later that year, he received orders to the JAG Trial Service Office Command South East at Naval Station Mayport, Florida, as a prosecutor.
- In 2006, he was promoted from lieutenant junior grade, to lieutenant. He worked for the commander of Joint Task Force-Guantanamo (JTF-GTMO), working directly with detainees at the Guantanamo Bay Joint Detention Facility.
- In 2007, DeSantis reported to the Naval Special Warfare Command Group in Coronado, California, where he was assigned to SEAL Team One and deployed to Iraq with the troop surge as the Legal Advisor to the SEAL Commander, Special Operations Task Force-West in Fallujah.
- DeSantis returned to the U.S. in April 2008, at which time he was reassigned to the Naval Region Southeast Legal Service. The U.S. Department of Justice appointed him to serve as an Assistant U.S. Attorney at the U.S. Attorney's Office in the Middle District of Florida. DeSantis was assigned as a trial defense counsel until his honorable discharge from active duty in February 2010.
- He was awarded the Bronze Star Medal, the Navy and Marine Corps Commendation Medal, the Global War on Terrorism Service Medal, and the Iraq Campaign Medal.
- On Discharch, he accepted a reserve commission as a Lieutenant Commander in the Judge Advocate General's Corps of the US Navy Reserve.
- He represented Florida's 6th Congressional District in the US House of Representatives from 2013 to 2018.
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