After graduation, Weatherford worked in commercial real estate but was recruited by Allan Bense, his father-in-law and the Speaker of the Florida House of Representatives, to join state government.

Weatherford's nomination apparently caused Brown, who had a history of mental illness, to suffer a breakdown, and he was admitted to the Harbor Behavioral Health Care Institute in accordance with the Baker Act.

[2] Over the course of the campaign, Weatherford massively outspent Brown and attacked him for his opposition to "jail time for people caught possessing small amounts of marijuana," about which he said that, because his name was not on the ballot, "he had to go negative or his district ran the risk of electing someone being treated for a mental disorder.

Weatherford was formally designated as the leader of Republicans in the Florida House of Representatives for the 2012-2014 legislative session in March 2011 following a vote in which he received the support of every single one of his colleagues.

[6] In 2013, Weatherford led the charge against the expansion of Medicaid provided for under the Patient Protection and Affordable Care Act, referring to it as "one of the worst forms of insurance you can get in America."

The 2013 Legislative session ended with approval[8] of priorities of both Weatherford and Senate President Don Gaetz, outlined in the historic "Work Plan Florida."