"I want to know, did General Flynn do this by himself or was he directed by somebody to do it?" Graham said in an interview with CNN's Kate Bolduan.
He said that he has not "seen the transcripts" of Flynn's conversations with with Russian Ambassador Sergey Kislyak before Trump took office.
"I think Congress needs to be informed of what actually General Flynn said to the Russian ambassador about lifting sanctions," Graham said. "Did he say anything at all or is this just being spun by the media?"
Flynn resigned from his role as White House national security adviser late Monday after questions arose about conversations he had with the Russian ambassador before Trump's inauguration.
Current and former U.S. officials told several news outlets last week that Flynn and Kislyak discussed U.S. sanctions during one call, contradicting members of Trump's administration, including Vice President Mike Pence, who previously denied that they did.
Graham said Tuesday that had "a hard time believing" Flynn would float the idea of lifting sanctions without "some understanding" that Trump's incoming administration would support that position.
"Maybe General Flynn went rogue, but that's a question I'd need to know more," Graham added. "I think most Americans have a right to know whether or not this was a General Flynn rogue maneuver, or was he basically speaking for somebody else in the White House?"
Graham said that he wants to know whether Flynn "was somehow compromised" by Russia.
"If somebody in the administration is subject to being blackmailed, I think that's something I'd like to know about," he said. "I think if the shoe were on the other foot we'd want to know the answers to these questions. Did General Flynn act alone?"