World championships

Guzmán became ranked number one in the super bantamweight division of the WBO. The WBO's world super bantamweight champion, Agapito Sanchez, travelled to Cardiff, Wales, to defend his title against Guzmán, but was diagnosed with a detached retina during a required medical check-up days before the fight and was then removed of the title. Sánchez temporarily retired from boxing and Guzmán found himself fighting Fabio Oliva for the vacant WBO's world super bantamweight title on August 17, 2002. Guzmán won the championship with a 3rd-round knockout win. Sánchez returned to boxing and at last fought Guzmán on February 26, 2004, in San Diego, California. Guzmán retained the title, knocking out the former world champion in seven rounds. He later defended that title, defeating previously unbeaten Fernando Beltrán by unanimous decision on April 22, 2005. Following his impressive victory, Guzmán moved to the super featherweight division.

At the weigh-in before his scheduled fight for the WBO super featherweight title on September 16, 2006, the title holder, Jorge Rodrigo Barrios, was overweight was eventually stripped of the WBO super featherweight title. Guzman then won the fight and the title by split decision. Guzman then defended his new title with wins over contender Antonio Davis on December 18, 2006, and future two division champion Humberto Soto on November 17, 2007, both by unanimous decision.

Move to lightweight

In May 2008, Guzman elected to vacate his WBO super featherweight title in order to continue his career in the lightweight division.^[2] He was supposed to fight for Nate Campbell's unified WBA super, WBO and IBF titles, on September 13, 2008. Disappointingly, he came in 3½ pounds over the 135 lb. limit.^[3] Thus, the fight was cancelled and Guzman was rushed to a hospital after experiencing dehydration and coughing blood.^[4] A dismayed Campbell who went through such trouble to fight him, branded Guzman's pull-out as an unprofessional gesture.^[5] With regards to his failure, Guzman issued an apology to his fans, people surrounding the scheduled bout, and to Campbell in particular.^[6]

On December 20, 2008, Guzman took on Ameth Diaz for the WBA lightweight title eliminator. Unlike his bout with Campbell, Guzman successfully made the weight limit.^[7] Guzman won his first-ever match as a lightweight by unanimous decision.

In an attempt to win a world title at a third weight division, Guzman challenged well regarded Ali Funeka on November 28, 2009, for the vacant IBF lightweight title. Unfortunately for both fighters, the bout resulted in a majority draw which most believed Funeka won by a wide margin.

Guzman and Funeka fought again on March 27, 2010, for the same championship. This time however, only Funeka had a chance to win the title as Guzman was 9 pounds above the lightweight limit. Nevertheless, the bout went on as scheduled. There, Guzman managed to score a knockdown as well as scoring enough points to win by split decision, leaving the belt vacant.

Light welterweight

Guzman's well documented struggles to make the 135 lb lightweight limit prompted him to move to junior welterweight. His first bout at 140 lbs against Jason Davis took place on the undercard of Amir Khan vs. Marcos Maidana on December 11 at the Mandalay Bay Resort & Casino in Las Vegas. The bout was ended by TKO in just the second round in the favour of Guzman, although he notably failed to make the weight for the second consecutive bout, coming in at 144.5 lbs

Positive testing drug controversy

In the post-fight drug test after the bout against Davis, however, Guzman tested positive for Furosemide, a diuretic banned by the Nevada State Athletic Commission, and the same kind used by Ali Funeka who was suspended for nine months after the rematch with Guzman.^[8] As a penalty, Guzman was suspended from boxing for eight months and his latest victory was turned into a no-contest.^[9] After complying with an eight-month suspension for, admittedly, having used a diuretic in an attempt to make weight for his fight against Jason Davis in December, 2010; Joan Guzman returned to the ring at 140 lbs. (Super lightweight) in his homeland, Dominican Republic, against Colombian Florencio Castellano in January 2012. Guzman knocked out Castellano in the first round, roughly 2:59 minutes into it. It was his first fight under the roster of Acquinity Sports (now Iron Mike Productions), a Florida-based promotion company, which has bet on the athlete's talent; and his first knock-out in at least ten fights(Excluding Davis's turned no-contest). On March 2, 2012, Guzman faced Puerto Rican Jesus Pabón. The fight was presented as the main event at ESPN2's Friday Night Fights. The event was named 'D-Day Dominican Domination' and featured several Dominican boxers, including Ed 'The Lion' Paredes and Juan Carlos Payano. Guzman came in for the first official weigh-in a quarter-pound heavier than the mandatory 140 lbs., needing two more attempts to finally make weight. However, Joan seemed pretty strong at 140. He knocked down Pabon in the very first round with a left hook; followed by consecutive knock-downs in the second and third rounds. Although Joan dominated all rounds, critics complained about his lack of 'killer instinct' and his showboating, which they say the ex-titlist might have used to hide the fact that he had grown physically tired. Pabon, even though he won no rounds, showed some guts in rounds five and six, landing a few good punches. In round eight, Joan came out strong again, and both boxers exchanged some punches. Pabon, the weaker of the two, was caught with a left hook that dropped him for good. Joan Guzman remained undefeated in 35 professional bouts. His record then stood at 33-0-1 and one No-contest (20 ko).

Unbeaten streak ends

On November 30, 2012, Guzman challenged Khabib Allakhverdiev for the IBO and vacant WBA super lightweight championship. The bout ended in the 8th round as Guzman hurt his knee which resulted from an accidental foul. The verdict was a technical decision in favor of Allakhverdiev. Guzman was knocked down in the third round, the result of a left; and blood readily flowing from the boxer's nose in the fifth set the momentum for the loss. The Sycuan Warrior did not show his trademark elusive style until it was practically too late in the fight. Only in rounds 6 and 7 did Guzman employ the kind of fighting technique that had kept him undefeated during his career. He circled, jabbed, and effectively counter-punched the Russian, evidently frustrating him. But, when in the 8th, he tripped and hurt his leg in the fall, Khabib responded with everything he had, setting the impression that he was the dominant fighter. Guzman could not go on due to the leg injury and the referee stopped the fight due to 'accidental foul', which led to the score cards deciding the winner. Two judges declared Khabib the better man on the ring. Talks of a rematch immediately ensued.^[10]