Markie's career began in the early 1980s as a performer, then a human beatbox for MC Shan and Roxanne Shante, among others. Biz Markie met producer Marley Marl in 1985, and began working as a human beatbox for Marl-connected acts MC Shan and, later, Roxanne Shant�. He also recorded his first set of demos, and by 1988, had signed with Cold Chillin'. Later that year, he released his debut, Goin' Off, which became a word-of-mouth hit based on the underground hit singles "Vapors," "Pickin' Boogers," and "Make the Music With Your Mouth, Biz".

A year later, he broke into the mainstream when "Just a Friend," a single featuring rapped verses and out-of-tune sang choruses, reached the pop Top Ten, and its accompanying album, The Biz Never Sleeps, went gold.

As one of the most prominent hip-hop stars of a still low-key musical scene, expectations were high for Biz's next album, I Need a Haircut. Sales were already disappointing when Biz was served a lawsuit by Gilbert O'Sullivan, who claimed that the album's "Alone Again" featured an unauthorized sample from his hit "Alone Again (Naturally)." O'Sullivan's claim was upheld in a ruling, Grand Upright Music, Ltd. v. Warner Brothers Records, Inc., that altered the landscape of hip-hop, finding that all samples must be cleared with the original artist before being used. In accordance with the ruling, Warner Bros., the parent company of Cold Chillin', had to pull I Need a Haircut from circulation, and all companies had to clear samples with the samples' creators before releasing the records. This development mirrored the increasing popularity of hip-hop and the financial stakes over which releases were set. Biz responded in 1993 with the mischievously titled "All Samples Cleared!", but his career had been hurt by the publicity emanating from the lawsuit, and the record suffered accordingly. For the remainder of the decade, he kept a low profile, guesting on records by the Beastie Boys and filming a freestyle television commercial for MTV2 in 1996 but otherwise remaining low-key and staying out of the spotlight. His affiliation with the Beastie Boys raised Biz's profile but Biz, during the late '90s and early '00s turned his attention more to the turntable than rapping.

Biz has also appeared on a record by Len, a Canadian rock/rap ensemble (known as the one-hit-wonder behind "Steal My Sunshine") and has guest-starred on albums by Morcheeba and by his friend Will Smith, most recently on his album Willennium.

One item of interest with regard to Biz has been the truthfulness of some of his claims about various musical and pop-culture miscellany which he has alleged he owns. He has bragged in interviews about toys, lunchboxes, videotapes and records that no one has ever heard of although he swears to his ownership of said items. Perhaps most significantly, the extent of his extensive vinyl collection has been called into question. He has claimed that it is stored 'in a building next to his house', although many have questioned this. Biz has also claimed he owns certain 12" singles of famous breakbeat records that were not formally released although this claim might be more plausible, given Biz' prominence within the industry and position as a pioneering hip/hop artist. Also supporting Biz' claims on this count is the fact that New York recordstore Downstairs Records pressed their own white label bootlegs of said records and which were widely respected within the hip-hop community. Another claim which Biz made and which was later shown to be false was that he inherited Lenny Roberts' entire collection (Ultimate Breaks And Beats compilation series) after he died. The range of falsehoods and possible truths about Biz' musical holdings only serve to enhance his legacy, and at least focus attention on a man with an undoubtedly significant role in the development of hip-hop. Since speculation about his holdings has died down, Biz quietly re-entered the very competitive recording industry with his 2003 release "Weekend Warrior" on Tommy Boy.

In 2005, Biz detoured from his recording duties to appear on the television show "Celebrity Fit Club", which challenged celebrities to lose weight by a combination of diet and exercise. Through a combination of luck and hard work, Biz won the competition.

Biz has also appeared in Men in Black II with Will Smith and Tommy Lee Jones.

Markie lost considerable weight after participating in the Celebrity Fit Club competition.He has also made a career as a DJ, giving performances where he uses his abdomen to move a record on a turntable and thus scratch. He is also a legendary record collector and supposedly the sole owner of a rare CTI 12" containing a version of Take Me To The Mardi Gras which has no bells in the intro.

He was also in an episode of The Andy Milonakis Show in 2005, in which he was the Rap Fairy who said, "I'm the Biz Markie, and it's about that time time I grant you the powers of rap and rhyme," granting Milonakis "rap powers" and demanded $35 from Milonakis, who paid him with potato chips and beef jerky.