By the late 1980s, Buffer was the exclusive ring announcer for all bouts in Donald Trump-owned casinos. Trump said of Buffer, "He's great, he's the choice, he has a unique ability...I told my people, 'We got to have him.'" Buffer's work was also admired by many boxing greats. Sugar Ray Leonard once said, "When [Buffer] introduces a fighter, it makes him want to fight."

In 1982, Buffer began his career as a ring announcer. By 1983, he was announcing all boxing matches promoted by Bob Arum's Top Rank on ESPN, which gave him a national identity at a time when ring announcers were strictly locally hired talent. By 1984, Buffer developed the catchphrase "Let's get ready to rumble" in his announcing, which gained enormous popularity. He began the process of obtaining a federal trademark for the phrase in the 1980s, acquiring it in 1992. Consequently, Buffer has earned in excess of $400 million with the license for his trademark.

Buffer began using the phrase "Let's get ready to rumble!" in 1984. By 1992, he acquired a federal trademark for the phrase. Buffer uses his famous phrase in various licensing deals including the platinum selling album Jock Jams by Tommy Boy Records, the video games Ready 2 Rumble Boxing, Ready 2 Rumble Boxing: Round 2 for the PlayStation 2, Nintendo 64, Dreamcast and Game Boy Advance and Greatest Heavyweights of the Ring for the Sega Genesis and numerous other products. In addition, he has used variations of the phrase in advertisements, including the popular commercial for Mega Millions in which he says "Let's get ready to Win Big!" and the Kraft Cheese commercial in which he says "Let's get ready to Crumble!" and most recently for Progressive Insurance in which he says "Let's get ready to bundle!" The phrase, "Are you ready to rumble?" is spoken in the 1957 television show Maverick, titled "Stage West" (episode 6, season one). by the stage coach driver to the passengers as he prepares to leave in the stage coach. As of 2009, the catchphrase has generated $400 million in revenue from licensing the trademark.

Buffer's fame has reunited him with long-lost family members. In 1989, Buffer was contacted by his birth-father, who introduced Buffer to his half-brothers after seeing him on television. In the mid-1990s, Buffer brought along one of his half-brothers, Bruce Buffer, as his agent/manager. This grew into a Business partnership to increase licensing productivity of the trademark.

Buffer, like his brother Bruce, announced early UFC fights, starting at UFC 6 in 1995. He was the host of Versus' boxing retro show Legends of the Ring, produced by Top Rank, Inc., where he was ring announcer for most of their top matches.

Buffer first wed at age 21 but the marriage ended in divorce after seven years. He has two sons from his first marriage. More than 25 years passed before he remarried in 1999. He and his second wife divorced in 2003.

Buffer was formerly the exclusive ring announcer for World Championship Wrestling (WCW) main events featuring Hulk Hogan or other top WCW talent until 2001, when the organization folded. WCW's former parent company Time Warner owned through their pay-per-view subscription division HBO, which broadcast many matches from promoter Top Rank, of which Buffer is the lead ring announcer. The exclusivity of his contract with WCW prevented Buffer from announcing for other wrestling-type organizations, forcing him to stop announcing for the UFC (his only UFC cards were UFC 6 and UFC 7). However, when WCW ceased to exist, and Time Warner had no more affiliation with professional wrestling, Buffer was enabled to announce in other wrestling promotions. During the Monday Night Wars, while Buffer was on WCW Monday Nitro, WWF Wrestler Triple H created the phrase "Let's get ready to suck it!" to mock him, as part of his D-Generation X act.

On September 13, 2007, while making an appearance on The Tonight Show with Jay Leno, he proposed to his current (third) wife, Christine. Buffer currently resides in Southern California. His half-brother Bruce Buffer is the announcer for leading mixed martial arts promotion, Ultimate Fighting Championship. Both Michael and Bruce are grandsons of late boxer Johnny Buff.

He has played himself in various films including Ready to Rumble and Rocky Balboa, and in 2008 Buffer appeared as Walbridge, the main villain in the comedy You Don't Mess with the Zohan.

Buffer appears as featuring Artist on "Let's Get Ready to Rumble" and "Go for It All!" by German eurodance group the K.O.'s and his voice was sampled in the Ant & Dec song "Let's Get Ready to Rhumble". He recorded the introduction track for country Artist Josh Turner's 2012 album, Punching Bag.

In 2013, Buffer appeared in Progressive Insurance commercials, promoting their program of combining different coverages into one policy, with a parody of his famous phrase - "Let's get ready to bundle!"

Buffer appeared at the University of Kentucky's men's basketball teams' legendary "Big Blue Madness" on October 14, 2016. Instead of his traditional "Let's get ready to rumble!" Buffer announced the beginning of the event with "Let's get ready to roundball!".