[3] In 1987, Musgrove ran for the District 10 seat of the Mississippi State Senate, representing Panola and Tate counties, which was being vacated by its incumbent.

[13] In 1995 Musgrove ran as the Democratic candidate for the office of lieutenant governor of Mississippi, facing one-term Republican incumbent Eddie Briggs.

[14] Briggs refused to debate his opponent, and Musgrove accused him of hypocrisy for not releasing his tax returns when he had demanded the same of Brad Dye, whom he had defeated four years prior.

[citation needed] After Fordice was gravely injured in a car accident, Musgrove served as acting governor from November 7 to December 17, 1996.

After the governor vetoed the Mississippi Adequate Education Act in 1987, Musgrove lobbied for the legislature to override Fordice's decision.

[25] Musgrove ran for the office of governor in 1999, having hired a full-time fundraiser and a political consultant to mount such a campaign two years prior.

[14] Musgrove focused on education advancements,[28][27] running a series of television ads showcasing his accomplishments as lieutenant governor in supporting elementary and secondary school improvements.

[29] He also ran a significant amount of campaign ads on Christian radio stations and espoused socially conservative positions such as opposition to abortion.

[35] Due to the short time frame between his election as governor and the date of his inauguration on January 11, 2000, Musgrove entered gubernatorial office with an incomplete staff.

[38] In August 2000, he launched the Advantage Mississippi Initiative (AMI) to create new jobs for the state, which brought in a new Nissan Motor Company production plant.

][38] Musgrove's AMI economic development package also helped set in motion the mechanics needed to recruit Toyota to Blue Springs.

[43] As a result, damage suit attorneys' political influence increased and by the early 2000s were one of the largest sources of campaign contributions for Democratic candidates in the state.

In late 2001, the press began to publish exposes on the damage suit attorneys, which, combined with a series of lawsuits against hospitals and medical practices, led to increased public support for reform.

[45] On August 23, 2002, Musgrove announced to a group of campaign contributors—all of them trial lawyers—his intention to call the legislature into special session to consider tort reform proposals.

[49][50] Despite the success of the session he had called, Musgrove garnered no obvious political advantage from the enactment of the reforms,[51] and Democrats' fundraising efforts in the state were left compromised.

[53] After losing his re-election bid Musgrove returned to private practice with the law firm of Copeland, Cook, Taylor & Bush, P.A.

On January 4, 2008, Musgrove confirmed that he would be a candidate in the 2008 United States Senate special election in Mississippi against Republican incumbent Roger Wicker.

Wicker eroded this lead by associating himself with conservative causes and attacking Musgrove as a liberal who had provoked budget issues during his gubernatorial administration and attempted to alter the state flag.

[57] Late in the race, polls indicated Wicker had a sizeable lead, though The Clarion-Ledger endorsed Musgrove, citing his support of education and child healthcare.

[57] Musgrove has remained active in public service since leaving office, continuing to serve on a number of boards and commissions that advocate for quality education and better access to health care for rural and low income families.

[59][60] As governor, Musgrove had conservative social views, enacting laws restricting homosexual couples from adopting children and requiring that the motto "In God We Trust" appear in all classrooms in Mississippi.

[72] In response to the ruling, Musgrove held a press conference to announce that he had issued an executive order creating a 17-member commission to study the flag.

[73] The commission eventually came up with a new design that replaced the battle flag in the canton with a circular array of twenty stars (Mississippi is the 20th state) on a blue background.