The paper had several questions for Rubio, including whether he can make "hard choices" on entitlements, offer a better alternative to Obamacare and clarify his views on climate change. The editorial board also said Rubio has recently "pandered to rising pessimism in his party."
"We hope Marco Rubio and his party take a different path, one that can lead to the opportunity and optimism he so eloquently articulates," the paper wrote.
For Clinton, the paper said in its endorsement of the former secretary of state
that she is a "thoughtful, hardworking public servant who has earned the respect of leaders at home and abroad. She stands ready to take on the most demanding job in the world."
The paper added, however, that Clinton is "not a perfect candidate," citing the scandal over her use of a private email server and what it said was a refusal to acknowledge mistakes.
"Her changing stance on gay marriage, immigration and other issues has invited accusations that she is guided less by personal conviction than by political calculations," the paper wrote. "She refutes that, and argues persuasively that a willingness to change one's thinking on specific issues, while remaining true to what she calls 'the same values and principles,' is a virtue, one lacking in most politicians."
Rubio's campaign did not immediately issue a public response to the Register's support. When a voter congratulated him Saturday night at a campaign event in Indianola, Iowa, Rubio responded, "Would rather have your endorsement. Still need you to caucus for me."
Clinton, however, told CNN after a campaign event in Davenport, Iowa, that she was "very pleased" to receive the endorsement.
"Obviously, it means a lot to me," Clinton said.
She later tweeted her appreciation.
"I'll work my heart out for Iowans and American families every day. Honored to have the @DMRegister's support—9 days to the caucus! -H" she said.
Although Clinton's main opponent, Vermont Sen. Bernie Sanders, didn't receive the Register's backing, his campaign came up with a clever way of capitalizing on the moment by purchasing advertising space on the paper's website when it announced its endorsements.
Jeff Weaver, Sanders' campaign manager, dismissed the importance of the Register endorsement on Saturday at the Scott County Democrats dinner in Davenport, Iowa.
"The person who didn't get the endorsement last time, eight years ago, won," Weaver said, referring to President Barack Obama. "So I am not sure what the significance is."
But, he added, "We would have loved to have the endorsement, obviously."
Paper interviewed nearly every candidate
Lynn Hicks, the Register's opinion editor, explained the endorsements to CNN's Poppy Harlow on Saturday.
"We felt that Senator Rubio has the chance, the opportunity, to chart a new direction for the Republican Party," Hicks said, adding, "We had questions about his experience, like a lot of people do, but we felt he was the best hope for the party, not only because he can attract independents, but his ideals can appeal to the base of the party and unify the party."
As for Clinton, Hicks said, "There's no question that she has the most experience, depth and breadth of knowledge and we really felt that she is the one that is prepared to help America face the many challenges that it faces."
The editorial board of the Register, Iowa's largest newspaper, interviewed every major 2016 Republican and Democratic candidate, some twice, with the exception of Trump and Cruz.
"They declined the board's invitation for an interview, but doing so did not disqualify them from consideration for the endorsement," according to a press release from the Register earlier this week.
The race has tightened considerably with Cruz leading Trump by just three points in a Register poll released last week. Clinton leads Sanders by just two points.
The endorsements are significant as many likely caucus-goers have not yet decided on a candidate. In Register polls released last week, 56% of Republicans and 40% of Democrats said they could still be persuaded to support another candidate as their first choice.
But the paper hasn't chosen caucus winners in recent years. In 2012, the paper endorsed Republican candidate Mitt Romney, and Sen. Rick Santorum won the caucuses by a slim margin. In 2008, the paper endorsed John McCain and Clinton, although Mike Huckabee and Barack Obama won in their respective parties.