The "Hardball" host on Tuesday labeled Cruz's marathon Senate speech on ObamaCare a publicity stunt and compared Cruz to a character in the movie "Dr. Strangelove" who rode a missile all the way down until it crashed and burned.
Matthews also drew comparison between Cruz and Joseph McCarthy for sharing a "smirk" and an "insulate look of moral condescension," and said Cruz's political career is bound to go up in flames.
He then called for "real patriot" Sen. John McCain (R-Ariz.) to defuse Cruz's efforts to defund the healthcare reform and save the GOP from embarrassment.
Cruz on Wednesday easily broke the record for the longest filibuster time for current Senators. Sen. Rand Paul (R-Ky.) previously held the record for the longest time, which was nearly 13 hours.
Although the Senate will still hold a procedural vote, Cruz vowed to continue to speak "until I am no longer able to stand."
On Matthews's show, Rep. Jim Moran (D-Va.) called Cruz a "phony" for preaching about helping the lower and middle class workforce. When he was at Harvard Law School, Moran said he refused to study with the "minor Ivy's" like Brown University or Dartmouth College.
"This guy is an arrogant elitist who is doing his best to manipulate a large part of the country who doesn't know any better," Moran said. "I think they're going to get on him pretty fast and realize what a phony he is."
Matthews agreed, and said he is unsure what Cruz is exactly trying to do as a Texas senator.
"He's not a legislator, he's not trying to pass bills," Matthews said. "He's not really trying to change government in the way that it is formulated and carried out.
"What is he actually trying to do?"