The most recent review of boundaries, passed through Parliament by means of the Northern Ireland Parliamentary Constituency Order sees no change to the boundaries of Fermanagh and South Tyrone. The electoral areas to make up this seat at the 2010 general election were:
The wards of Augher, Aughnacloy, Ballygawley, Ballysaggart, Benburb, Caledon, Castlecaulfield, Clogher, Coolhill, Drumglass, Fivemiletown, Killyman, Killymeal, Moy, Moygashel, and Mullaghmore from Dungannon and South Tyrone district
Throughout its history, Fermanagh and South Tyrone has seen a precarious balance between unionist and nationalist voters, though in recent years the nationalists have had a slight majority. Many elections have seen a candidate from one community triumph due to multiple candidates from the other community splitting the vote.
Perhaps because of this balance between the communities, Fermanagh and South Tyrone has repeatedly had the highest turn-out of any constituency in Northern Ireland.
The seat was initially won by the Nationalist Party in 1950 and 1951, the closely contested 1951 election seeing a 93.4% turnout – a UK record for any election.
In 1955, the constituency was won by Philip Clarke of Sinn Féin, but he was unseated on petition on the basis that his criminal conviction (for IRA activity) made him ineligible. Instead, the seat was awarded to the Unionist candidate.
Republicans suffered a reversal in the 1983 general election, when the SDLP contested the seat. Maginnis won and held the seat for the UUP for the next eighteen years until he retired. By this point boundary changes had resulted in a broad 50:50 balance between unionists and nationalists and it was expected that a single unionist candidate would hold the seat in the 2001 general election. James Cooper was nominated by the UUP. On this occasion, however, it was the unionist vote that was to be split. Initially Maurice Morrow of the Democratic Unionist Party (DUP) was nominated to stand, with the DUP fiercely opposing the UUP's support for the Good Friday Agreement. Morrow, then withdrew in favour of Jim Dixon, a survivor of the Enniskillen bombing who stood as an Independent Unionist opposed to the Agreement. Dixon polled 6,843 votes, 6,790 in excess of the 53 vote lead that Sinn Féin's Michelle Gildernew had over Cooper. Subsequently, the result was challenged amid allegations that a polling station had been kept open by force for longer than the deadline, allowing more people to vote, but the courts – while conceding that this happened, did not uphold the challenge because it held that the votes cast after the legal closing time would not have affected the outcome.
Ahead of the 2005 general election, there was speculation that a single unionist candidate could retake the seat. The UUP and DUP, however, ran opposing candidates and in the event Gildernew held her seat. She kept the seat in 2010 by four votes over the Unionist candidate, Rodney Connor. Following the election, Connor lodged an election petition challenging the result based on a dispute about differences in the number of ballot papers recorded at polling stations and those subsequently recorded at the count centre. The petition was rejected after it was found that only three extra votes remained unnaccounted for. The judge ruled that "even if those votes were introduced in breach of the rules and if they had all been counted in favour of the first respondent their exclusion would still have given the first respondent (Ms Gildernew) a majority of one vote and the result would not have been affected."