Saad Muhammad began to box professionally in 1974, with a two round knockout win against Billy Early. He posted seven more wins that year, before suffering his first loss, at the hands of Wayne McGee by a decision in six.
In 1975, he had two wins and then he and McGee fought again, that time around, resulting in a six round draw.
In 1976, Saad Muhammad had a major step up in opponent quality: He faced future world champions Marvin Camel and Mate Parlov, both of them twice. His first fight with Parlov, in Milan, was also his first fight abroad. He beat Parlov by an eight round decision. He then beat Camel by a ten round decision, but lost to him by a ten round decision in a rematch. After returning to Italy for a rematch with Parlov, he and Parlov struggled to a ten round draw.
He began 1977 by losing to Mustafa Muhammad (then Gregory), but he quickly turned things around by facing the future three time world champion Marvin Johnson, for the United States Light-Heavyweight title. In his first national television exposure, Saad Muhammad ended up winning that brawl by a knockout in round 12, obtaining the regional championship.
In 1978, the wins kept on coming: He won all four of his bouts that year and defended the United States title against former world title challenger Richie Kates and against four time world title challenger Alvaro Yaqui Lopez. The Lopez fight, their first of two, was considered a classic by boxing experts, and Saad Muhammad survived a relentless attack by Lopez to retain the belt with an 11th. round knockout.
By 1979, Johnson had become world champion by defeating Parlov, and Saad Muhammad felt he deserved a chance at the world title. So, on April 22, they met for a second time, this time in Johnson's hometown of Indianapolis. This fight was also considered by many experts as a Saad Muhammad classic, and has been shown on ESPN Classic's Classic Fights show. Saad Muhammad won the WBC's world Light Heavyweight crown with an eight round knockout of Johnson, after staggering him with a right hand towards the end of the seventh round.
For his first defense, he met former world champion John Conteh in Atlantic City. He retained the world title with a 15 round decision. The decision, however, was unpopular and an immediate rematch was ordered, so they met again, this time Saad Muhammad retaining the crown with a knockout in round four. After beating Louis Pergaud, he and Lopez met again, this time, with the world title on the line. Their rematch has also been shown by ESPN's classic network several times, and it was the fight of the year for 1980, according to Ring Magazine. Saad Muhammad was hit with 20 unanswered blows in round eight, but he recovered and dropped Lopez five times in route to a 14th round knockout win. It was around this time that he formally changed his name from Matthew Franklin to Matthew Saad Muhammad.
He then went on to defeat Lotte Mwale, Vonzell Vampire Johnson, future world Super-Middleweight champion Murray Sutherland and Jerry Martin, all in defense of his world title, before facing Muhammad Qawi (then Braxton) in December of 1981. In yet another fight that would later by shown on ESPN's classic network, Saad Muhammad lost his title when Qawi knocked him out in 10 rounds.
Saad Muhammad entered 1982 with a rematch against Qawi within his sights, and he defeated Pete McIntyre by a knockout in round two. The rematch between Saad Muhammad and Qawi came off in August, at Saad Muhammad's hometown of Philadelphia. The second time around, Qawi won by a knockout in round six.
From there on until 1992, Saad Muhammad fought sporadically and with limited success. He had been confronting eyesight problems, and in 1986, he declared himself in bankruptcy. He did, however, fight in many countries around the world between the moment he lost the rematch to Qawi and the moment he retired for good. Among those countries were Australia, Spain, The Bahamas and Trinidad and Tobago.
Saad Muhammad retired with a record of 39 wins, 16 losses and 3 draws, with 29 wins by knockout.
In 2001, he became a member of the International Boxing Hall of Fame.