"A lot of Texas Tech fans think he's to blame for the loss," suggested Kimmel on Tuesday, noting that Cruz attended the game.
The late-night host then pointed to a tweet Cruz posted during the fourth quarter.
"35 seconds. ONE point LEAD. GO RED RAIDERS!!! #1 Defense," the senator tweeted, along with a selfie.
"The moment he posted it the game was in overtime and the Red Raiders lost," continued Kimmel, as the audience roared with laughter.
The comedian then explained that this has happened to Cruz before.
Last year, Kimmel said Cruz was also blamed for the Houston Rockets' Game 7 loss in the western conference NBA finals.
"And back in 2017, I remember he posted, 'Congrats to Lori Loughlin daughter's acceptance into USC - well-deserved!" Kimmel then joked, putting up a spoof tweet of Cruz posing in front of a school statue.
"And we all know what happened with that, so ... Poor Ted," added Kimmel, referring to Loughlin's alleged involvement in the multimillion-dollar college admissions cheating scam.
Cruz didn't directly respond to Kimmel, though he did comment on whether or not he's a "jinx" for popular sports teams.
"Ah, Leftie snark. Tech did great last night, but haters gonna hate. I was there & cheered the Astros on in 2017; I cheered the Spurs on in 2014; I cheered UT on in the Rose Bowl in 2005; and I cheered the Rockets on in 1994. We won them all — that kind of 'jinx' is pretty good!" replied Cruz on Tuesday to an article titled, "Did Ted Cruz jing Texas Tech with late-game tweet?"
Loughlin and her fashion designer husband, Mossimo Giannulli, were among 14 people indicted on fraud and money laundering charges Tuesday in the scandal. The couple is accused of forking over $500,000 to ensure their two daughters, Isabella, 20, and Olivia Jade, 19, would get accepted into the University of Southern California as crew team recruits — despite allegedly never having actually participated in the sport.
Celebrities across the Hollywood spectrum have mocked Loughlin as well as "Desperate Housewives" actress Felicity Huffman after their alleged roles in the scheme surfaced.
Fox News' Sasha Savitsky contributed to this report.