Wylde started playing the guitar at the age of 15 and worked at Silverton Music in Silverton, New Jersey. He grew up in Jackson and went to Jackson Memorial Highschool where he graduated from in 1985. Zakk has stated that he would practice playing the guitar as much as 12 hours per day and often would play the guitar almost non-stop between coming home from school and leaving for school the next morning, then sleeping through the school day.

Growing up Wylde played locally with his first band, "Stone Henge", then later with local Jersey band "Zyris". Years later, the then unknown 20 year-old Wylde landed the coveted role as lead guitarist and co-writer for Ozzy Osbourne. He sent Ozzy a demo tape in 1987 and was hired to replace Jake E. Lee. Jake E. Lee had replaced the deceased Randy Rhoads, an idol of Wylde's, for whom he even built a shrine.

Wylde's then-girlfriend (now wife) Barbaranne heard Ozzy was looking for a new guitarist on the Howard Stern radio show. While playing at a local gig, a photographer spoke to Wylde urging him to audition for Ozzy, and offered to send a presskit along to Osbourne; Wylde, who at the time was working at a local Getty gas station, decided he had nothing to lose. Ozzy dismissed the tape among thousands of others as "just another Randy Rhoads clone". But a couple of weeks later, Randy Castillo, Ozzy's drummer at the time told him he'd found a great guitarist from New Jersey. Wylde recalled how he received a phone call from Sharon Osbourne (thinking it was one of his friends' mother) telling him there was a ticket for him to fly out and audition for Ozzy. Wylde has said that he was hired on the spot before even playing, while he was still tuning his guitar. The truth of this is unknown as Wylde is known for joking with interviewers. The first material he released with Osbourne was No Rest for the Wicked in 1988.

Zakk Wylde's guitar-playing style is characterized by his use of pinch harmonics and wide/aggressive vibrato. His guitar soloing technique is usually characterized by use of the minor pentatonic scale, playing rapid box-pattern licks using strict alternate-picking, creating a very distinctive, choppy style of playing. Another notable feature of Wylde's playing is his liberal use of "chicken pickin' ," a technique which is usually associated with country music, and which is (comparatively) rarely seen in heavy metal; a technique he has stated as being picked up from watching Albert Lee.

He is known for his use of Gibson Les Paul Custom model guitars with a unique "bulls-eye" graphic on them, a design he used to deliberately differentiate himself visually from Randy Rhoads - who was also frequently identified by his white Les Paul Custom. Interestingly, one of Wylde's favorite stage guitars of late is a replica of Rhoads' Flying V. The "bulls-eye" paint job was originally supposed to look like the spiral from the movie Vertigo, but when it came back incorrect from the luthier, he liked the result and stuck with it.

Wylde's signature Les Paul's include, a red and flame-maple bulls-eye model, a black and antique-white bulls-eye model, an orange "buzz-saw" model, which Zakk got the pattern off a zippo lighter , and a "camo" bulls-eye model with mother of pearl neck inlays and a green camouflage paint scheme. His original bulls-eye Les Paul was bought from a regular store front and is christened "The Grail". It was lost to Wylde for some time when it fell off the truck as he was coming back from a gig in Texas. Rewards were posted to anyone that had information about the guitar - it holds sentimental value to him since it was a gift from his parents.

Wylde and The Grail were only reunited years later, after a fan bought it at a pawn shop and realized he may very well have the missing guitar after checking the initials "Z.W." on its back and the serial number marked on the headstock. He then contacted Wylde's former webmaster Randy Canis to arrange its return.

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