Santos turned professional when he was 20 years old and began his career 2-0 before facing legendary Brazilian fighter Jose "Pele" Landi-Jons, losing by TKO. Santos won his first two fights with the British Cage Rage organization before returning to Brazil's Jungle Fight, winning over future KSW Middleweight Champion Michal Materla by knockout, which is Materla's only knockout loss of his career to date. Santos then fought against Dutch kickboxer Melvin "No Mercy" Manhoef for the Cage Rage World Light Heavyweight Championship. The two fought a highly-entertaining bout, trading punches but Santos ultimately lost after being knocked out. Santos won his next two fights, including a majority decision over future UFC veteran Francis Carmont before making his debut in PRIDE FC.
Santos made his debut in Japan's PRIDE FC against submission specialist Kazuhiro Nakamura, losing by a keylock submission. His next fight with the Japanese organization was against Japanese professional boxer Yosuke Nishijima, which Santos won by a rear-naked choke submission.
Santos fought again for the Cage Rage World Light Heavyweight Championship against James Zikic but lost by unanimous decision. Santos also lost his next fight against Armenian superstar Gegard Mousasi by TKO before making his debut in World Victory Road Presents: Sengoku Raiden Championships against Makoto Takimoto, winning by an achilles lock. Santos fought once more for the Japanese organization against future UFC veteran Siyar Bahadurzada, losing by TKO after receiving an arm injury.
Santos made his Strikeforce debut June 19, 2009 and headlined the Strikeforce Challengers: Villasenor vs. Cyborg event, but came up short against former King of the Cage Middleweight Champion Joey Villasenor losing by a split decision. In his next fight, he went on to face and defeat Marius Zaromskis, who battled Nick Diaz for the vacant Strikeforce Welterweight Title.
Santos challenged Strikeforce Welterweight Champion Nick Diaz for the title on January 29, 2011 at the HP Pavilion in San Jose, California. He lost the fight via armbar submission in the second round.
Santos was due to fight Paul Daley at Strikeforce: Fedor vs. Henderson but was forced to withdraw due to a shoulder injury. Santos fought Strikeforce newcomer Jordan Mein on September 10, 2011 at Strikeforce World Grand Prix: Barnett vs. Kharitonov. After a grueling back and forth fight "Cyborg" was defeated by Mein via TKO due to Elbows in the third round handing "Cyborg" back to back defeats, Santos has now suffered his fourth loss in his last six fights.
After a long period of inactivity, Santos requested his release from Strikeforce to fight more consistently. His request was granted.
Santos was expected to face Pete Spratt at Legacy Fighting Championship 17 on February 1, 2013. However, Santos was forced to pull out of the bout due to injury and was replaced by Dan Hornbuckle.
After nearly two years away from the sport, Santos returned to face Artenas Young in the main event during Legacy Fighting Championship 50 on January 22, 2016. He won the fight by unanimous decision.
Santos made his GSF debut on April 28, 2014, against Melvin Manhoef in a rematch from 2006. Santos, who was knocked out by Manhoef in their first outing, lost to Manhoef again via first-round knockout. Santos then announced his retirement shortly after the fight.
On March 1, 2016, it was announced that Santos signed a multi-fight contract with Bellator MMA.
Santos made his organizational debut April 22 on the main card of Bellator 153 in a welterweight matchup beating Brennan Ward via first round submission.
Making a quick turnaround, Santos agreed to fight Saad Awad at Bellator 154 on May 14, 2016 but lost.
On July 16, 2016, Santos faced Michael "Venom" Page and was defeated via KO by a flying knee, resulting in a frontal sinus fracture which required seven hours of surgery.
Santos retired in January 2017. He "will continue running Chute Boxe’s gym in Texas, and also head the Minas Gerais’ muay thai federation. “Cyborg" will also focus on working with young amateur and professional athletes in Uberlandia, Minas Gerais."
Santos was married to Women's MMA fighter Cristiane Justino, but the couple split in December 2011.