After all, he opposed his own state's initiative to legalize pot in 2012.
But the first-term senator has since defended Colorado's decision, and in the past 24 hours he's become the face of a bipartisan effort that has him butting heads with the Trump administration.
At 8:58 a.m. ET Thursday, Gardner learned through Twitter of a Justice Department decision that would soon lead him to the Senate floor with a fiery speech railing against the attorney general.
He was furious that Jeff Sessions had rescinded a memo that adopted a policy of non-interference with marijuana-friendly state laws.
Critics, like Gardner, say the move violates states' rights and causes uncertainty in legal marijuana industries.
It also goes against a campaign promise that Donald Trump made in 2016, when he told a Colorado news station
the state should be allowed to keep observing its marijuana laws. "I think it's up to the states, yeah. I'm a states person," Trump said at the time. "I think it should be up to the states, absolutely."
On the Senate floor Thursday, the usually mild-mannered Gardner was outraged, calling the decision "a trampling of Colorado's rights, its voters." He vowed to put a hold on every Justice Department nominee until Sessions reverses course.
He also said the decision by Sessions broke a personal pledge the former Alabama senator had made to Gardner before his confirmation last year: "I would like to know from the attorney general: What changed?"
Gardner spoke briefly with Sessions by phone afterward and the two men plan to meet soon, according to a Gardner aide.
It was the second time in recent months that the senator has very publicly gone against members of his party.
But Gardner, who hails from a state with a libertarian streak, is still a largely reliable vote for Republicans. He holds a leadership position in the caucus as chief of the Senate GOP campaign arm. Despite landing in the headlines recently for challenging those in his own party, it's unlikely he'll join the small chorus of Republicans who've become outspoken critics of President Trump, a la Sens. Jeff Flake of Arizona and Bob Corker of Tennessee.
Still, it was just months ago that Gardner led the risky charge to expel a potential Republican colleague.
As chairman of the National Republican Senatorial Committee, he released a bombshell of a statement
in November shortly after The Washington Post reported allegations of sexual abuse against Roy Moore, the Republican nominee in the Alabama US Senate special election.
Gardner said if Moore "refuses to withdraw and wins, the Senate should vote to expel him." While many Republicans in the Senate urged Moore to drop out of the race, none of them had publicly gone as far as Gardner in saying Moore should be expelled if he were elected.
Even when the Republican National Committee decided to resume its support for Moore's campaign, despite cutting ties just weeks earlier, Gardner and the NRSC held fast. "Roy Moore will never have the support of the senatorial committee," Gardner told The Weekly Standard. "I won't let that happen. Nothing will change. I stand by my previous statement."
When Moore was defeated days later in an upset win by Democrat Doug Jones
, Gardner didn't need to follow through with his call to expel Moore: "Tonight's results are clear -- the people of Alabama deemed Roy Moore unfit to serve in the US Senate."
Gardner has also joined Flake and Sen. Lindsey Graham of South Carolina in working heavily with Democrats to pursue a deal on immigration -- and has stood apart from his party leadership in supporting Graham and Democratic Sen. Dick Durbin's legislation that would make the Deferred Action for Childhood Arrivals program permanent.
Elected to the Senate in 2014, Gardner, 43, was previously a two-term US congressman and a member of the Colorado House of Representatives. He served as a congressional staffer early in his career.
In the Senate, he's sought to build up his foreign policy credentials as a member of the Foreign Relations Committee, with a focus on North Korea. He is also a member of the Energy and Natural Resources Committee, the Commerce, Science, and Transportation Committee, and the Budget Committee.