Debut in Germany

Gamboa made his professional boxing debut on 27 April 2007, in Hamburg, Germany against Alexan Manvelyan.^[4] He prepared for his pro debut and his next seven fights with technical specialist Manny Masson. Gamboa put Manvelyan on the canvas in the third round and won via unanimous decision victory. Two months later, he defeated Araik Sachbazjan when Sachbazjan retired before the beginning of round four.

Debut in the United States

After winning his first four fights in Germany, Gamboa made his United States debut on 30 October 2007, at the Seminole Hard Rock Hotel and Casino in Hollywood, Florida, against Adailton De Jesus, who was dropped to the canvas halfway through the first round. A Gamboa slip in the fourth round was ruled a knockdown by the referee. Gamboa's relentless pressure eventually forced a stoppage in the sixth and final round.^[5]

Gamboa fought Gilberto Luque on 5 January 2008, at Bally's Hotel & Casino in Atlantic City, New Jersey. Gamboa sent his opponent to the canvas less than 30 seconds into first round with a left hand. After two more knockdowns, the referee stopped the fight.^[6] On 22 February 2008, in Fort Lauderdale, Florida, he made his American television debut against Johnnie Edwards. Gamboa knocked Edwards down in the first 30 seconds of the fight after connecting with a left hand to the head. Edwards got up, but was met with left-hand punches from Gamboa, ending with two consecutive right hands that knocked Edwards down for the second and final time as the referee moved in and halted the fight in round one. Gamboa won the vacant WBC-NABF super featherweight title.^[7]

On 17 May 2008, at Buffalo Bill's Star Arena in Primm, Nevada, Gamboa fought Darling Jimenez. Gamboa started off well in the first three rounds of the fight, swarming Jimenez and hitting him with punches over and over but got careless and was knocked down by a right hand behind the ear from Jimenez. Gamboa got up and finished the fight strong, winning by unanimous decision and claiming the vacant WBC International super featherweight title.^[8] After the fight, Gamboa's promoter Ahmet Öner fired Gamboa's trainer Osmiri Fernandez, replacing him with Ismeal Salas.^[9] On 18 July 2008, stepping down to featherweight, Gamboa scored a first-round technical knockout (TKO) victory over Al Seeger to win the vacant WBO-NABO featherweight title at Buffalo Bill's Star Arena. A left hook to the body set up a right hand that landed across Seeger's face, causing him to collapse backwards flat onto the canvas. The referee stepped over Seeger without bothering to count, officially stopping the bout.^[10]

On 5 October 2008, Gamboa stepped up in class and fought Marcos Ramirez, a Kansas City featherweight in Temecula, California. Gamboa exhibited amazing hand speed and quick combination punching in the first round before he was dropped by Ramirez. Gamboa quickly came to his feet and resumed fighting until the bell rang to signify the end of the round. In the second round, Gamboa picked up where he left off and knocked Ramirez down with a fast right uppercut, followed by another combination. Ramirez let the referee administer the eight count before rising to his feet. Gamboa then finished the fight by pressuring Ramirez into the ropes and landing a left hook to the body, followed by a right uppercut to the jaw.^[11] Gamboa's next fight took place at Buffalo Bill's Star Arena on 9 January 2009 against Roger Gonzalez. Gamboa used quick combinations from the beginning of the third round to relentlessly attack Gonzalez. Gamboa began his assault after going down during the second round, after absorbing a sneaky right hand by Gonzalez. The referee halted the one-sided bout with 48 seconds remaining after Gonzalez sustained a barrage of punches to the head. Gamboa led 89–82 on one judge's scorecard and 89–83 on the other two judges' cards through nine rounds.^[12]

On 20 February 2009, Gamboa fought Walter Estrada at The University Center at Nova Southeastern University. Gamboa knocked out Estrada with a left hook to the body followed by a right hand to the face 25 seconds into the fight.

Featherweight

On 17 April 2009 Gamboa stopped Jose Rojas via tenth-round TKO to win the WBA interim featherweight title.^[13] On 10 October 2009 Gamboa stopped Whyber Garcia in the fourth round to win the WBA featherweight title.^[14]

On 23 January 2010, at the WaMu Theater in Madison Square Garden, he defeated Rogers Mtagwa in two rounds. Gamboa buzzed Mtagwa several times from several angles and scored a knockdown in the final ten seconds with a counter hook. He continued the damage in the second round, battering Mtagwa and sending him down two more times before the fight was stopped. On 27 March 2010 at Hamburg, Germany Gamboa dominated Argentinian boxer Jonathan Victor Barros in twelve rounds to retain the WBA featherweight title with a unanimous decision.

Super featherweight

After the 50 Cent-Mayweather TMT Promotions never came to fruition, 50 Cent decided to make his own promotional company SMS Promotions and officially signed Gamboa. 50 Cent worked with Top Rank's Bob Arum and Mayweather's rival Manny Pacquiao. Gamboa then landed a fight on the undercard of Manny Pacquiao vs. Juan Manuel Márquez IV on 8 December 2012. He fought Michael Farenas, who fought to a draw in his previous fight with WBA title holder Takashi Uchiyama. Gamboa was show boating throughout the fight while Farenas maintained his focus. Farenas was dropped twice which gave Gamboa more confidence, dropping his hands occasionally. In the ninth round Gamboa tried to finish Farenas off with a barrage of punches but Farenas countered him with a left hook that dropped Gamboa. Gamboa stopped show boating after the ninth round, winning the fight by unanimous decision.^[17]

Performance-enhancing drug scandal

As he was moving up to lightweight, Gamboa was linked to performance-enhancing drugs through the Biogenesis scandal, which included Alex Rodriguez.^[18]

Lightweight

Gamboa eventually moved up in weight to take on undefeated Darleys Pérez (28-0) for the vacant WBA interim lightweight title. Gamboa dropped Pérez in the first round and easily won most of the follow-up rounds, Yuriorkis continued to have success on the outside winning almost all the middle rounds as well. Gamboa although fighting at an unusually measured pace at times consistently beat Pérez to the punch amassing a clear lead in the bout. Pérez came alive momentarily to drop Gamboa in the eleventh but this was ruled a slip and Yuriorkis Gamboa won a comfortable unanimous decision improving to 23–0.