Ahead of its passage, Rubio slammed the bill in a Thursday television interview.
“I know enough to say we’re going to oppose it, and I know enough to say that we should use every procedural aspect that we have to slow it down and perhaps force some changes on these things that we've been discussing," he said on Fox News Channel.
The bill is among the most significant Congress has passed this year. It includes a $1.1 trillion spending portion and a $622 billion tax section. Many fiscal conservatives rallied against it.
Rubio is in the midst of a busy week of fundraising and campaigning. On Friday, he is holding public events in Iowa and Missouri. A study by Vocativ and Govtrack earlier this year found Rubio to be the most absent member of the Senate.
In a Friday interview with CBS News, Rubio said of the bill, "In essence, not voting for it is a vote against it."
"Votes like Friday's are why Marco is running for president," said his campaign spokesman, Alex Conant. "Leaders in Washington crafted this trillion-dollar spending bill in secret, and unveiled it during the debate on Tuesday night. Marco had barely 48 hours to review over 2,000 pages of spending. Marco has consistently voted against those sorts of bills, but the truth is that it's not going to change until we elect a new president. That's why Marco is meeting voters in Iowa today."
While Rubio was not in the Capitol to voice his outrage in person, he issued a statement through his Senate office.
“Washington's leadership has created another massive spending bill in secret and rammed it through Congress, hoping that the American people don't notice or have become numb to this kind of business as usual," he said.