In 1978, Spinks won two fights, including an eight round decision over former world Middleweight title challenger Tom Bethea, in the same undercard where his brother Leon dethroned Ali as world Heavyweight champion in Las Vegas.
1979 saw Spinks get less than three minutes of boxing action inside a ring, with his only fight ending in a first round knockout of Marc Hans, but in 1980, Spinks took his ascent towards the top to another level, when he beat future world Super Middleweight champion Murray Sutherland, David Conteh and fringe contenders Ramon Ronquillo and Alvaro Yaqui Lopez (who challenged for a world title four times). Of his five wins that year, three came by knockout, Sutherland and Johnny Wilburn being the only ones who lasted the distance.
By 1981, Spinks was already a top ranked contender, and after beating former and future world Light Heavyweight champion Marvin Johnson by a knockout in four rounds, the WBA made Spinks their number one challenger, and so, on July 18 of that year, he met WBA's Light Heavyweight champion Eddie Mustafa Muhammad, once again in Las Vegas. Spinks dropped Mustafa Muhammad in round 12 and went on to become world Light Heavyweight champion with a 15 round decision win. He defended the title once in '81, beating Vonzell Johnson by a knockout in seven.
After four successful defenses in 1982, including a knockout win in eight in a rematch with Sutherland, Spinks had become a superstar, at least in the boxing world. He began appearing on the covers of boxing magazines and boxing fans started clamoring for a unification fight with WBC world champion Dwight Muhammad Qawi. Tragedy struck his life, however, when in January 1983, his girlfriend died in a car crash, leaving Spinks the single parent of his two-year-old daughter.
Meanwhile, the fight all the fans wanted was being asked for by boxing critics and magazine editors, too. On March 18, two months after his girlfriend's death, Spinks and Qawi met in a boxing ring. The fight was broadcast by HBO World Championship Boxing, and, according to the book The Ring: Boxing the 20th Century, Spinks had a very tough moment to overcome before it even started: His daughter asked him, while he was in his dressing room, if her mother would come to watch the fight. Spinks almost broke into tears, but soon had to recover and get into the ring, where he and Qawi fought to unify the crown. Spinks was floored in round eight, but he got up and won a 15 round majority decision to become the undisputed world Light Heavyweight champion. He defended the title one more time before the end of the year, against Oscar Rivadeneira in Alaska, whom he beat by a ten round knockout.
Spinks fought only once in 1984, retaining his crown with a twelve-round majority decision over Eddie Davis. He and Qawi were only a couple of weeks away from fighting a rematch in September of that year, but that fight got called off when Qawi was injured during training.
In 1985, Spinks beat David Sears and Jim McDonald, both by knockout, in title defenses, before challenging Larry Holmes for the world's Heavyweight championship in a fight recognized by the IBF. Holmes was trying to tie Rocky Marciano's record of 49-0 as the Heavyweight champion, but it was Spinks who made history that night, winning a fifteen-round unanimous decision and becoming the first world Light Heavyweight champion ever to win the world Heavyweight title. With this, Michael and Leon had also become the first pair of brothers ever to be world Heavyweight champions.
In 1986, Spinks and Holmes fought a rematch, and had nearly the same result, this time Spinks winning by a 15 round split decision. After that, he retained the world Heavyweight championship once again, by a knockout in four against Steffen Tangstad. In 1987 he was stripped of the crown by the IBF for refusing to fight their mandatory challenger, Tony Tucker, and accepting a higher offer to fight Gerry Cooney in a non title bout instead. Spinks knocked out Cooney in five rounds, and after Mike Tyson had unified the Heavyweight belts, fans started clamoring for a fight between them as many still recognized Spinks as the legitimate champion. The fight took place in June 1988, with Tyson knocking Spinks down twice on his way to a first round knockout. It would be Spinks' first defeat in the ring, as well as his last as he retired following the fight.
Spinks had a record of 31 wins, 1 loss and 21 wins by knockout as a professional.
On Ring Magazine's list of 100 greatest punchers of all time, Spinks ranked was 42nd.
On Ring Magazine's list of the 80 Best Fighters of the Last 80 Years, released in 2002, Spinks ranked 41st.