Romero, who is a born again Christian, had a gang-related life before finding Christianity. The fact that he and hometown arch-rival Johnny Tapia, now also a Christian, were involved with rival gangs and they were world champions at the same weight, during the same time, made boxing fans talk about a fight between the two long before it actually took place.

Romero's first fight as a professional was on September 14, 1992, when he knocked out Raul Hernandez in the first round at Phoenix, Arizona. His first eight bouts all took place in the Phoenix area, and he won all, seven by knockout. His first fight outside Phoenix was on April 13, 1993, when he knocked out Alberto Cantu in three rounds at Bay St. Louis, Mississippi. On May 22 of that year, he had his first professional fight in his hometown, knocking out Silverio Porras in two rounds.

Danny Romero won five more bouts in a row, including a victory over former Alex Sanchez world title challenger Orlando Malone, before having his first chance to fight for a belt: On May 5, 1994, he knocked out Brian Lonon in two rounds to win the NABF regional Flyweight title.

He retained the title four times, and added three non-title victories, before challenging for a world championship for the first time. On April 22, 1995, he became the IBF's world Flyweight champion with a twelve round unanimous decision over Francisco Tejedor, at the MGM hotel, in Las Vegas, Nevada. He defended the title once, then faced the unheralded Willy Salazar in a non-title bout, on September 8. Romero suffered a 7th round TKO loss to Salazar, in what Ring Magazine heralded as the "upset of the year" for 1995. In that fight he was ahead on all score cards before having the fight stopped due to an eye injury. He bounced back with a first round knockout victory over former WBO world Flyweight champion Jose Quirino.

Romero then decided to move up in weight division, to the Super Flyweight division. After one win in that division, he was given a chance at his second world championship. On August 24, 1996, Romero knocked out Colombian Harold Grey in two rounds to conquer his second world title. Even as he had lost to Salazar previously, interest in a fight between Romero and Tapia began to increase.

After winning two more fights, both times Romero retaining his world title by knockout, Romero and Tapia met to unify the IBF and WBO world Super Flyweight championships. Albuquerque police announced previous to the fight, that they were prepared for any gang related violence to take place on the streets of Albuquerque during fight night, but the only incident involving members of Tapia's and Romero's gangs happened 33,000 feet over the ground, as two members of the conflicting gangs coincided in a Southwest Airlines flight to Las Vegas, where the fight was held at. It was a minor incident and no further gang related violence occurred. On July 18, 1997, the long-awaited bout finally took place, with Tapia winning a twelve round unanimous decision, to inflict Romero his second career defeat.

Romero won three fights in a row, then lost, on Halloween night, 1998 to Vujani Bungu by a twelve round decision in an attempt to win a title in a third division, this time the IBF Super-Bantamweight title.

Romero would go on to win ten of his next twelve bouts, including a first round knockout over former world champion Rodolfo Blanco and a sixth round knockout over the respected Famosito Gomez. But when he was given a second chance to become a two time world Bantamweight champion, on September 27, 2002, he was knocked out in four rounds by Cruz Carbajal for the WBO world Bantamweight title. Romero had begun to proclaim his Christianity to the public long before the Carbajal fight.

On May 23, 2003, he retired, in front of his hometown crowd, with a twelve round unanimous decision win over Trinidad Mendoza that gave him the IBA's Super-Bantamweight title.

He retired from boxing after that victory. He retired with 44 wins, 5 losses and one draw (tie), with 37 of those wins coming by knockout. Romero did occasional television jobs, specifically for the Showtime boxing network.

After retiring Romero Jr.'s father was stricken with a rare liver disorder, a form of cirrhosis that would kill him without a transplant. On death's doorstep, Romero Sr. received a liver transplant from his youngest son, Juan Romero. Inspired by his father's battle, Romero Jr. returned to the ring and, fighting for the first time in two years, was held to a majority draw by Alex Ali Baba (21-7-1) in an eight-round junior featherweight fight.