He boxed professionally for the first time on February 10, 1919, fighting Dominic Orsini to a four round no-decision in Elizabeth, New Jersey. As a matter of a fact, his first seventeen bouts were all boxed in Elizabeth. For his eighteenth bout, he went to Newark. On April 29 of 1919, he was defeated by knockout in round one by K.O. Phil Delmontt, suffering his first defeat.
In 1920, he boxed twelve times, winning two and participating in ten no-decisions. Once again, all his bouts were held in New Jersey, which was, at the time, one of the areas where scoring systems had not been installed in boxing, therefore, each fight that lasted the scheduled distance was automatically declared a no-decision, regardless of who the better boxer had been.
He boxed sixteen times in 1921, winning six, losing one and having nine no-decisions. By then, Rhode Island had already become one of the areas where scoring in fights had been installed to allow fighters to get decision victories, and this attracted Walker twice to the area. He lost on a disqualification to Joe Stenafik his first time there, but earned his first decision win, in twelve rounds, against Kid Green, the second time around. He also held world champion boxer Jack Britton to a no-decision back in his home state of New Jersey, and beat Nate Siegal in Boston.
1922 was not looking like a great year for Mickey Walker, as he went 3-4-4 before getting a world title shot. He lost to Jock Malone during that span. However, on November 1 of that year, he found himself a world title challenger against Britton, who was the world's Welterweight champion. Walker outpointed Britton over fifteen rounds to become world champion.
Nine bouts followed in 1924, Walker winning six and having three no decisions. He defeated Lew Tendler and Bobby Barrett in defense of his world title, and had two of his three no decisions that year against arch-enemy Jock Malone.
After winning two fights to start 1925, he went up in division to challenge world Middleweight champion Harry Greb on July 2 but he failed to win the Middleweight crown at that time, losing a fifteen round decision to the 160 pound division champion. He went back to the Welterweight division, defending his title against Dave Shade, retaining it by decision. He won three bouts, lost one and had three no decisions that year.
On May 20, 1926, he lost the world Welterweight title in a rematch with Pete Latzo, concentrating on winning the world Middleweight title instead after that. On November 22, he finally was able to beat Jock Malone, and on December 3, he conquered the world's Middleweight title with a ten round decision over world champion Tiger Flowers. He kept that title for five years, although he only defended it three times during that span. He beat Mike McTigue and former world champion Paul Berlenbach.
On March 28, 1929, he tried to become a member of the exclusive group of boxers who have been world champions in three different weight divisions, however, he failed in his attempt when he was defeated by a ten round decision by world Light Heavyweight champion Tommy Loughran. On June 19, 1931, Walker decided to give away his world Middleweight title to take a leap into the Heavyweight division. His debut as a Heavyweight on July 22, against former world Heavyweight champion Jack Sharkey, ended with a fifteen round draw (tie). In 1932, he went 5-1, beating such fighters as King Levinsky and Paulino Uzcudun before facing former world Heavyweight champion Max Schmeling, who knocked Walker out in round eight.
He went down in weight again, to the Light Heavyweight division, in 1933, when he lost a fifteen round decision to Maxie Rosenbloom for the world title. He kept campaigning in that division until 1935, when he retired after losing to Eric Seelig by a seven round technical decision.
He became, however, an accomplished painting artist, many of his works being exhibited at New York and London art galleries. During his boxing career, he found golf to be a suitable distraction to his training regimen, and he often dragged his manager Doc Kearns, and his kids to golf courses to play golf. There is a golf course named after him.
Walker was found by police in 1974 lying on a street in New York and taken to a hospital, where he was admitted with doctors initially thinking he was just a drunken man picked up at the streets. But further testing revealed that Walker was suffering from Parkinson's disease. Walker ignored who he was or where he was at when he was picked up by the police officers.
While he recovered from this incident, Parkinson's eventually took his life, and he died seven years later.
Walker had a record of 93 wins, 14 losses, 4 draws, 46 no decisions and 1 no contest in 163 professional bouts, his 60 knockout wins making him a member of the exclusive group of boxers who have won 50 or more bouts by knockout.