Cisco announced his decision Tuesday evening in a Twitter video.
The preseason first-team AP All-American from Long Island entered the season with 12 interceptions, the most in the FBS, and snared another before suffering a lower-body injury in a collision with a teammate in pregame warm-ups just over two weeks ago. He missed the Orange's past two games.
"At one point, I did not think I would make it this far," Cisco says on the video. "The road to this point was not easy. These past few years have been unbelievable. Since the moment I stepped on campus it felt like a dream.''
Coach Dino Babers said Cisco was out for the season a day before the junior star made his announcement.
"This is something I've been dreaming of since I was 8 years old," Cisco said. "I've given the school everything I've got and this community gave it back tenfold. I can't wait to make you all proud.''
Cisco finishes his Syracuse career as a two-time All-Atlantic Coast Conference selection and was the only freshman named to the Walter Camp All-America team after his breakout rookie campaign.
Cisco became the first true freshman defensive back to start a season opener at Syracuse since Markus Paul in 1985. He led all FBS players in interceptions with seven his first season, the first true freshman to lead the country in the category since Oregon's George Shaw had 13 in 1951.
Cisco earned AP third-team All-American honors for his performance and followed that by leading the ACC with five interceptions in nine games as a sophomore.
"He's a guy that you want guys to look up to,'' redshirt senior offensive lineman Chris Elmore said Tuesday night. "He wants the guys to come up to him. He's just a really good leader. He definitely was different, him coming in and starting as a true freshman.''