The remarks by retired Marine General James Mattis were the latest by one of Trump's Cabinet picks that veered away from the president-elect's campaign rhetoric, which included praise for Russian President Vladimir Putin and pledges to improve ties with him.
Secretary of State nominee Rex Tillerson on Wednesday also expressed views at odds with Trump on key foreign policy issues like nuclear proliferation, trade deals, climate change and relations with Mexico.
Mattis said Russia, China and terrorists were presenting the biggest challenge to the “US-led world order” since World War Two, and called for Congress to lift spending caps undermining military readiness, Reuters reported.
"I'm all for engagement but we also have to recognize reality in what Russia is up to," Mattis said, adding there were a "decreasing number of areas" where the United States might cooperate with Moscow.
Asked about the main threats to US interests, Mattis said: "I would consider the principle threats to start with Russia."
Mattis said he wanted to meet with the new Trump national security team to "craft a strategy to confront Russia for what it's done," when questioned about the possibility of new US sanctions.