Trump signed the legislation behind closed doors and away from the cameras, after failed efforts to scupper or water down the bill.
Trump's reluctance was on full display in an angry signing statement, in which he called the legislation "significantly flawed."
"In its haste to pass this legislation, the Congress included a number of clearly unconstitutional provisions," he said, including curbs on the president's ability to conduct foreign policy.
The legislation -- which also includes measures against North Korea and Iran -- targets the Russian energy sector, giving Washington the ability to sanction companies involved in developing Russian pipelines, and placing curbs on some Russian weapons exporters.
It also notably constrains Trump's ability to waive the penalties, a statement of mistrust from the Republican controlled Congress which remains unsettled by Trump's warm words for President Vladimir Putin.
The sanctions seek to penalize the Kremlin for meddling in the 2016 US presidential election -- which Trump won -- and Russia's annexation of Crimea.
Trump said he would "honor" some of the bill's provisions, but stopped short of saying it would be fully implemented.
The White House said only that Trump would give Congress's "preferences" mere "careful and respectful consideration."
Trump received the legislation at 1:53 pm on Friday and waited until Wednesday to sign it.
By signing it, he avoided the humiliating prospect of Congress overriding his veto.
Expecting the signature, Moscow preemptively ordered Washington to reduce its diplomatic presence in Russia to 455 persons before September 1 -- bringing it in line with the size of Russia's mission in the US.
US Secretary of State Rex Tillerson said Tuesday he will meet with his Russian opposite Foreign Minister Sergei Lavrov over the weekend, but warned US-Russia ties could still get worse.
"The question, I think, of the events of the last week or so, is it getting worse or can we maintain some level of stability in that relationship?" Tillerson asked.
Tillerson said the US Congress's decision to pass the sanctions bill had made attempts to thaw ties "more difficult."
A special prosecutor is investigating whether Trump advisers colluded with what US intelligence has concluded was an attempt by Russia to covertly support his 2016 campaign.
The US president, who often called for warmer ties with Moscow during the White House race, has furiously denied the charge, which has further clouded relations.