Incumbent Democratic senator Bill Nelson ran for re-election to a fourth term, but was narrowly defeated by Republican governor Rick Scott.

The results showed that Nelson was narrowly trailing Scott, but the margin remained below 0.5%, triggering an automatic recount under Florida law.

Scott's victory marked the first time since the Reconstruction era in 1875 that Republicans have held both Senate seats in Florida, making it the last former Confederate State to do so.

[5] Despite having won re-election in 2012 by a 13% margin, Nelson was considered potentially vulnerable; he had been the only statewide elected Democrat in Florida since 2011, and his previous opponents, Connie Mack IV and Katherine Harris, were seen as much weaker challengers than Scott.

[6] After being encouraged by President Trump to enter the Senate race,[7] Republican governor of Florida Rick Scott announced his candidacy on April 9, 2018.

[66][67] Scott's involvement in a large Medicare fraud case stirred controversy during the general election campaign.

Nelson also mentioned the Orlando nightclub shooting that occurred in June 2016 and killed 49 people, asserting that "nothing was done" by Scott's administration.

Scott and his administration had been heavily criticized for weakening regulations designed to protect the environment, even going as far as to instruct the FDEP not to use the words "climate change" or "global warming" in official reports.

[73] Because of this, Scott was blamed for the state's worsening algae blooms, even being dubbed "Red Tide Rick" on social media.

[76] Both Nelson's and Scott's responses to Hurricanes Irma and Michael (which made landfall in September 2017 and October 2018, respectively) were closely watched during the campaign season.

As the race was determined by less than 10,000 votes, some have speculated that the ballot design flaws contributed to the election outcome.

[305][306] Notably, election officials in Broward County had to receive police protection after accusations of voter fraud were made by a few members of Congress.

[307] Additionally, a number of mail-in ballots were found in a mail distribution center in the city of Opa-locka three days after the election.