White attended Baylor University in Waco, Texas, where he was a member of the Tryon Coterie Club (now the Texas Lambda Chapter of Phi Delta Theta). He subsequently graduated from Baylor Law School in 1965.
White served as the state's assistant attorney general. In 1973, White was appointed as Texas secretary of state under Governor Dolph Briscoe and also served in the 36th Infantry Division of the Texas National Guard.
White served as secretary of state until 1977, when he resigned to run for state attorney general, where he served until 1983. In the 1978 general election, White defeated the Republican choice, James A. Baker, III, a Houston Lawyer, businessman, and power broker affiliated with the Bush family of Houston. White polled 1,249,846 votes and (55.13 percent) to Baker's 999,431 votes and (44.08 percent).
As the state's chief enforcement officer, he co-chaired the Federal-State Enforcement Coordinating Committee and was a member of the Governor's Organized Crime Prevention Council. On the national level, he was elected Chairman of the Southern Conference of Attorneys General in May 1981.
White declined to seek a second term as state attorney general, but chose to seek the governorship in 1982 against fellow Democrat Bob Armstrong, who was the outgoing state Land Commissioner, who vacated the General Land Office following twelve years, and then the incumbent Bill Clements, Texas' first Republican governor since Reconstruction. In November 1982, he defeated Clements over concerns about the governor's poor economic numbers and lack of support from minority groups. White received 1,697,870 votes (53.2 percent) to Clements' 1,465,537 (45.9 percent) in a year where Texas Democrats swept all the statewide offices up for grabs; led by U.S. Senator Lloyd Bentsen (who won a third six-year term to the Senate) and the legendary Lieutenant Governor of Texas william P. Hobby Jr..
Among White's appointments was Elma Salinas Ender as the first Hispanic woman to serve as judge of a district court in Texas. From 1983 until her retirement in 2012, Ender was judge of the 341st Judicial District, based in Laredo.
When he took office, Texas was ranked as one of the lowest performing states for the Scholastic Aptitude Test (SAT) also in teachers' salaries. After taking office, White immediately appointed a committee on Public Education, called a special session of the legislature in 1984, and worked with lawmakers to pass the Educational Opportunity Act (EOA).
White served as governor during Texas' sesquicentennial in 1986 and oversaw a number of the celebrations concerning that anniversary.
In the 1986 gubernatorial election, White lost to former Republican Governor Clements, 52.7% to 46.0%. Some believe that the wildly unpopular "no-pass, no-play" policies of the White administration, which prohibited any high school student athletes from participating in varsity Sports if they were failing any single element of their overall class load, sealed the doom of a second term. Clements polled 1,813,779 votes (52.7%) to White's 1,584,515 votes (46.1%) in the November 1986 general election and left office on January 20, 1987.
Following his departure from office, White worked for the law firm Keck, Mahin & Cate. White attempted to run for governor again in 1990, but he was defeated in the Democratic primary by Ann Richards, who then defeated Jim Matt Ox in a runoff election and the Republican Clayton W. Williams, Jr., in the general election. During the 1990 campaign, a campaign commercial depicted White "walking down a hallway displaying larger-than-life photos of the men put to death during his administration in 1983-1986. 'Only a governor can make executions happen,' White declared as ominous music played in the background. 'I did, and I will.'"
White practiced law and was chairman of the board of the Houston Independent School District Foundation, a non-profit organization which supports the public schools. White endorsed Houston City Council candidate Jolanda Jones in the 2003 and 2007 city elections. The latter endorsement helped lead to Jones winning an at-large seat on the council. He also endorsed then-United States Senator Barack Obama (D-Illinois) in the Texas primaries for the 2008 Democratic Presidential nomination, which Obama went on to win the presidency.
In 2011, White publicly opposed Texas A&M's potential departure from the Big 12 conference to join the Southeastern Conference (SEC).
Mark White Elementary School, a Houston Independent School District elementary school, opened in August 2016.
On August 10, 2017, White's remains lay in state for three hours in the Texas State Capitol. Luci Baines Johnson, daughter of U.S. President Lyndon B. Johnson, paid tribute to her friend White, whom she said "may have left public office, but he never left public Service. ... He welcomed the big tent of folks. He was not a divider; he was a unifier."
Mark White's son Andrew announced a run for Governor of Texas in 2018. In the March 6, 2018 Democratic Party primary, he placed second, forcing a runoff with Lupe Valdez scheduled for May 2018.