Edwards and his wife, the former Donna Hutto (born February 1967), have two daughters, Sarah and Samantha Edwards, and one son, John Miller Edwards. John Bel Edwards is a regular parishioner of the St. Helena Roman Catholic Church in Amite. Edwards is the brother of Independence, Louisiana chief of police Frank Millard Edwards, as well as Tangipahoa Parish Sheriff Daniel H. Edwards. Edwards is brother-in-law to 21st Judicial District Court Juvenile Judge Blair Downing Edwards, a Republican. In 2014, Edwards and other members of his Tangipahoa Parish political family were inducted as a group into the Louisiana Political Museum and Hall of Fame Winnfield.

Edwards was born and raised in Amite, Louisiana, the son of Dora Jean (née Miller) and Tangipahoa Parish Sheriff Frank M. Edwards, Jr., a member of the administration of Louisiana Governor Edwin Edwards (no known family relation). Edwards graduated from Amite High School in 1984 as valedictorian. In 1988, Edwards received a bachelor's degree in engineering from the United States Military Academy, where he was on the Dean's List and served as vice chairman of the panel that enforced the West Point honor code.

Edwards completed Airborne School in 1986, while he was a student at West Point. After receiving his commission, he completed the Infantry Officer Basic Course at Fort Benning (1988), Ranger School (1989), and the Infantry Officer Advanced Course (1992). Edwards served in the Army for eight years, mostly in the 25th Infantry Division and 82nd Airborne Division, including commanding a company in the 82nd's 3rd Battalion, 505th Parachute Infantry Regiment. He ended his military career to return to Louisiana because of family considerations. Edwards earned a law degree from the Louisiana State University's Paul M. Hebert Law Center in 1999, and he was a practicing attorney with the Edwards & Associates Law Firm in Amite. As an attorney, Edwards handled a variety of cases, though he did not practice Criminal law because of his brother's status as the local sheriff.

Edwards is a conservative Democrat who is pro-life and pro-gun rights. In 2008, Edwards ran for a seat in the Louisiana House of Representatives. Edwards was forced into a general election run-off with fellow attorney George Tucker. Edwards was overwhelmingly elected, winning every parish in the district. Edwards was the only freshman lawmaker to chair a committee in the legislature. Edwards chaired the Veterans Affairs Committee in the House. Edwards was also selected as chairman of the Democratic house caucus, a rarity for a freshman legislator. Edwards became a critic of Governor Bobby Jindal for the governor's frequent trips away from Louisiana to raise political funds for Republicans elsewhere while Louisiana has been reducing its funding for higher education.

In 2011, Edwards was re-elected to the Louisiana House of Representatives, having defeated opponent Johnny Duncan, 83 to 17 percent. Edwards served as chairman of the Louisiana House Democratic Caucus, making him the Louisiana House Minority Leader. Cities/towns that Edwards represented included Amite, Greensburg, and Kentwood as well as part of Hammond.

Meanwhile, the Republican Governors Association entered the Louisiana campaign in support of Vitter with an advertisement highlighting Edwards' past support for President Barack Obama, who twice lost Louisiana's electoral votes. Edwards was a delegate for Obama at the 2012 Democratic National Convention. Edwards supported Hillary Clinton in the 2016 presidential election.

On February 21, 2013, Edwards announced that he would run for governor in 2015. He said that his state needs "a healthy dose of Common sense and compassion for ordinary people". The only major Democrat in the race, Edwards polled first in the nonpartisan blanket primary with 444,517 votes (39.9 percent), followed by Vitter, who finished second with 256,300 votes (23 percent). In third place was Louisiana Public Service Commissioner Scott Angelle of Breaux Bridge, who received 214,982 votes (19.3 percent).

The governor also rescinded another executive order issued in 2015 by his predecessor, Bobby Jindal, which protected businesses and nonprofit organizations who oppose same-sex marriage from being legally punished for holding those views. This order had prohibited state agencies from penalizing businesses and individuals who act from a “religious belief that marriage is or should be recognized as the union of one man and one woman."

On April 13, 2016, Edwards signed an executive order to protect lesbian, gay, bisexual, and transgender people from harassment or job dismissals. The order prohibits state agencies from discrimination based on either gender identity or sexual orientation. The order allows an exception for religious organizations who claim that compliance would violate their religious beliefs. "We respect our fellow citizens for their beliefs, but we do not discriminate based on our disagreements. I believe in giving every Louisianan the opportunity to be successful and to thrive in our state," Edwards said.

In February 2017, Edwards and other state officials went to Italy, where he met with Pope Francis.