Fighting at welterweight, Collins won his first 14 fights as a professional, among them a decision win over future world title challenger Harold Brazier. On 16 June 1983, he was matched against Puerto Rican-born boxer Luis Resto at Madison Square Garden on the undercard of the Roberto Durán vs Davey Moore light-middleweight title fight. Collins entered the fight as a heavy favorite, but suffered a severe beating, losing by a unanimous decision. At the end of the bout Collins' father and trainer, Billy, Sr., noticed that Resto's gloves felt thinner than normal and demanded that they be impounded. Even without this to consider, it was obvious that someone had tampered with the gloves. Collins' eyes had been swollen shut, and the rest of his face was badly swollen as well. Many who saw pictures of Collins after the fight felt it was impossible for the light-punching Resto to inflict such damage on his own.

The subsequent investigation by the New York State Boxing Commission concluded that Resto's trainer, Panama Lewis, had removed an ounce of padding from each glove. The fight was ruled a no-contest. Lewis was effectively banned from any official role in American boxing for life, while Resto was suspended for at least a year and never fought again. In 1986, Lewis and Resto were tried and convicted of assault, conspiracy, and criminal possession of a deadly weapon (Resto's fists); prosecutors felt that Lewis' actions made the fight an illegal assault on Collins. Both men served 2.5 years in prison.

During the fight Collins had suffered a torn iris and permanently blurred vision, which prevented him from boxing again. After losing two jobs in a short time after the fight he began smoking marijuana and drinking heavily. His violent mood swings threatened his marriage. Finally, on March 6 1984, he crashed his car into a culvert near his home in Antioch, Tennessee; a suburb of Nashville. He was killed on impact. Many commentators, as well as Collins' family, believe that the loss of his livelihood broke him psychologically.

In July 1983, Collins and his family sued Lewis, Resto, fight promoter Top Rank Boxing, the inspectors, the bout's referee and Everlast (the manufacturer of Resto's gloves) for gross negligence and loss of income. However, the suit was derailed by Collins' death. Collins, Sr. and Collins' widow Andrea then sued the New York State Boxing Commission for failing to protect Collins. The commission argued that the term "inspection" was so broad that there was no way to determine whether the fight's inspectors could have done more than they did. It also claimed that Top Rank actually hired the inspectors and bore more responsibility for their behavior. A court ruled in favor of the commission, and the court also noted that Collins' death ended any potential future damages. However, Collins' widow, now known as Andrea Collins-Nile, is trying to reopen the suit. The state subsequently changed its rules to prevent a repeat of what happened to Collins.

In 2007, Resto made a tearful apology to Collins-Nile for his role in the scheme. He also admitted that his hand wraps had been soaked in plaster of Paris before the fight. This caused them to harden into plaster casts like those used to set broken bones. The hand wraps were never confiscated and did not figure into the official investigation of the tampering incident. However, the net result was that between the plaster casts and unpadded gloves, Resto was striking Collins with rocks. At a 2008 press conference, Resto not only admitted to knowing that Lewis had tampered with the gloves, but had done so at least twice before.

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