After several wins and only a single draw later, Guerrero won the WBC NABF Featherweight title against Cesar Figueroa on December 9, 2004.
Defending his NABF title twice, Guerrero was seen as a rising prospect, until meeting Gamaliel Diaz in a bout televised on ShoBox, on the Showtime channel, on December 12, 2005.
Guerrero rebounded from his first loss by defeating Sandros Marcos via third-round technical knock-out, setting up a rematch against Diaz, again on Showtime.
In his first world championship fight on September 2, 2006, Guerrero defeated Eric Aiken by an eighth-round technical knockout in Los Angeles.
[3] However, Salido would subsequently be stripped of the IBF title after testing positive for steroids, thus vacating the belt; the result of the bout would also be changed to a twelve-round no decision by the Nevada State Athletic Commission.
The IBF subsequently gave Guerrero the shot at the vacant featherweight title, which he won by ninth-round technical knockout in Copenhagen, Denmark on February 23, 2007, against Albanian boxer Spend Abazi.
[11] On July 31, 2010, Guerrero moved up to the junior welterweight division and faced Cuban fighter Joel Casamayor on the undercard of the Marquez vs. Diaz pay-per-view at the Mandalay Bay in Las Vegas.
Guerrero was scheduled to face Marcos Maidana in August for the WBA junior welterweight title, however, he was forced to pull out of the bout after suffering a torn tendon in his rotator cuff.
[15] Guerrero returned to the ring by jumping two weight classes to face unbeaten top 10 welterweight Selcuk Aydin.
On July 28, 2012 Guerrero defeated Aydin in San Jose, California by unanimous decision for the interim WBC welterweight title.
[16] Guerrero's next fight was against former two-time Welterweight champion Andre Berto (28–1, 22 KO) at the Citizens Bank Business Arena in Ontario, California.
[23] On March 7, Guerrero fought in NBC's first episode of their new series, "Premier Boxing Champions" at the MGM Grand in Las Vegas.
Ultimately, "The Ghost" lost by unanimous decision but Guerrero's determination and strong will to win had the crowd of the MGM Grand chanting his name for the majority of the final round.
[24][25] On June 6, 2015 Guerrero fought again on NBC as part of the "Premier Boxing Champions" series at StubHub Center, California, against the gritty Aron Martinez (19–4–1, 4 KOs).
Martinez continued to press the action in Round 4, scoring a knockdown at the end with hard body shots and then combinations to the head.
Both fighters had their moments in the latter half of the fight, but it was Guerrero who was able to control the distance, outland Martinez and pull out a split-decision win in a feisty back-and-forth battle.
[26] On January 23, 2016 Guerrero fought on FOX as part of the "Premier Boxing Champions" series at Staples Center, California, against the undefeated Danny Garcia (31–0–0, 18 KO) for the vacant WBC Welterweight Championship.
The match was ruled a unanimous decision in favor of Garcia with all three judges scoring the bout 116–112, despite fighting on near-equal terms.
[27] Guerrero's next fight was announced on July 16, to take place at the Honda Center in Anaheim against Argentine boxer David Emanuel Peralta (25–2–1, 14 KOs) on August 27.
[28][29] On May 23, 2017 it was announced that Guerrero would fight at the renovated Nassau Coliseum in Uniondale, New York against undefeated former WBC lightweight champion Omar Figueroa Jr. (26–0–1, 18 KOs) on July 15, 2017.
The bout will take place as part of a triple header main event which would include Sean Monaghan vs. Marcus Browne.
[33][34] On November 8, 2018 Guerrero surprisingly announced he would be returning to the boxing ring, stating he had 'some fight left' and also wanting to further his legacy.
According to ESPN, his return bout would take place on December 1 on the Wilder vs. Fury Showtime PPV card at the Staples Center in Los Angeles, California.