Born in the Bronx, young Andre was one third of The Harlem World Crew, along with Alonzo Brown and the late DJ Ronnie Green (who also recorded under the name "Captain Rock.") Alonzo told The Foundation that he met Andre when they were students at Charles Evans Hughes High School in Manhattan.

"Andre was in my brother's technical electricity class and that's how we met. This was in the late 1970s before rap records," he remembered. "I was already writing rhymes after seeing Lovebug Starski at the Renaissance Hotel (affectionately known as 'The Renny.') I'd asked my mother to buy me a microphone because I was writing rhymes to the intro of Barry White records—because his intros went on forever." Alonzo explained that Harrell, (who was from Bronx River Projects), was hearing Hip-Hop in the Bronx from the likes of Busy Bee and Afrika Bambaataa's Bronx River crews. The two developed a bond playing cards in the lunch room of Charles Evans Hughes.

Their mutual love of music—rap music specifically—strengthened their friendship, and led to them forming a group and performing at various community centers in Harlem's Clinton Projects after rhyming in the staircases at school. Although Harrell had connections in the Bronx, he hung out more in Harlem after meeting Alonzo.

"Harlem is fly, maybe he preferred it for that reason," Alonzo said. "I also think that he wanted to be downtown. Hip-Hop was really happening in Harlem at this point. Also, the biggest Harlem Hip-Hop spots were in my neighborhood. Dewitt Clinton Projects, where I lived, was right next to Schomberg, where Rayvon and them were (Johnny Wa and Rayvon of Harlem's Magnificent 7.) I could walk to (legendary early Hip-Hop club) Harlem World; and Chuck Center, Clinton Center and Foster Center were all in my neighborhood. That's the reason why you would see my name on those community flyers without Andre, even though we were a group. I lived in Harlem, and he lived in The Bronx."

Because of their proximity to, and time spent at Harlem World, Jeckyll & Hyde made recordings that were financed by Harlem World's Fat Jack on Tayster and Rojac Records. Their first record was "Rappers Convention," released under the name "Harlem World Crew." It was an uptempo song based musically on "Hooked On Your Love" by The Fantastic Aleems of NIA Records fame. "Rappers Convention" contained the typical braggadocio that every rap record made in 1980 contained, except for a verse by Mr. Hyde about the Iran hostage situation and the resulting high gasoline prices. This would mark one of the earliest times that serious political commentary was contained on a rap recording. Although it had national distribution, "Rappers Convention" remained an underground New York rap record—original pressings have become something of a collectors' item.

In 1980, under the name "Lonnie Love," Alonzo released a song called "Young Ladies" that was picked up by Profile Records, which at the time released dance music. Profile co -founder Cory Robbins told ROCK THE BELLS that the recording indirectly saved the struggling label.

"Running a label wasn't as easy as we thought. In the first six months we almost went out of business," he recalled. "We didn't have any big hits. We put out a few records that didn't do that well. In 1981, we decided to release a record based on Tom Tom Club's 'Genius of Love' called 'Genius Rap'. We didn't know that many rappers, but we had released "Young Ladies" by Lonnie Love the year before and we asked him did he wanna do 'Genius Rap.' He said that he'd only do it if he could bring Andre along and we did it. We recorded it on a Monday and gave Mr. Magic of WBLS a tape of it, and he played it that Saturday. It was our first hit record, it sold about 150,000 copies."

During their time at Profile, (which was from 1981 through 1986), Dr. Jeckyll & Mr Hyde also released "The Challenge." The song is musically based on "Nasty Girls" by Vanity 6; and they also dropped the Pumpkin-produced "Gettin' Money;: the Kurtis Blow-produced "AM-PM"/"Fast Life;" and the full-length album The Champagne of Rap. They also appeared on "Here Comes That Beat," credited to Pumpkin and The Profile All-Stars featuring The Fresh 3 MC's, The Disco 4, and Dr. Jeckyll & Mr. Hyde. Andre was also working with Russell Simmons and his Rush Productions/Rush Artist Management, and later Def Jam Records, at the time. Although they are never referenced by name, both Alonzo and Andre appear throughout the semi-autobiographical Krush Groove motion picture which fictionalizes Russell Simmons' early career in music.

The image of Dr. Jeckyll & Mr. Hyde possibly held them back with the more hardcore elements of the rap audience, but if "dressing for the job that you want, not the one that you have" had spokespersons, then Alonzo and Andre would have the gig. Where their contemporaries wore tracksuits, sneakers and rope chains, Jeckyll & Hyde wore dress suits and hard-bottomed dress shoes. On their full length album The Champagne of Rap, not only are they dressed in suits; they are holding copies of The Wall Street Journal and business magazines along with their DJ Scratch On Galaxy. Even the title of the album implies that they are more refined than other emcees. On "Cold Chillin' In The Spot" (which is the B side to "The Def Jam" by DJ Jazzy Jay), an animated Russell Simmons says to Andre, who is present in the studio: "The Doctor? Dr Jeckyll? Nigga, whats wrong with you—in a three-piece suit and a button down shirt?"

"We all had jobs at the time," Brown says. "Rap wasn't big enough yet where that's all you did. Andre worked at a radio station WINS selling air time to different business in New York, and I was a runner at the American Stock Exchange. I would literally take orders and run across the trading floor. We both had to wear suits to our jobs, but it all comes down to aspiration. Watching television I always wanted to be the guy on the other side of the desk, and I never wanted to be influenced by somebody else's whim. I didn't want to necessarily be a boss, but I wanted to be in control. There wasn't a ton of opportunities for black men in business, but living in New York you saw it. If you rode the train, you're standing next to a motherfucker who could be a millionaire!"

By 1986, Dr. Jeckyll and Mr. Hyde were done recording for Profile as a group, and Dr. Jeckyll (Andre) was releasing Uptown's Kickin' it, the compilation album that served as an introduction to his new label, Uptown Records. Uptown is the term that New York natives use to identify Harlem. The album introduced Heavy D & The Boyz, Finesse & Synquis, Groove B. Chill, The Brothers Black, and Woody Rock. DJ Marley Marl also contributed a song to the album titled "He Cuts So Fresh." The title track was a posse cut featuring verses from each emcee on the label after Andre's proclamation: "I'm funky fresh Dr. Jeckyll, cold coolin'on the place and I'm chillin wit my new group goin' Uptown—we gettin' money baby!"

Heavy D's first song "Mr. Big Stuff," which was produced by Harrell and Heavy's DJ Eddie F. was featured on this very compilation. Uptown eventually secured a 50 million dollar deal with its parent company MCA Records.

Uptown Records would launch the careers of stars like Jodeci, Father MC, Guy, Al B Sure! and Mary J Blige. Harrell actually went to Blige's home in the Schlobohm projects in Yonkers, N.Y. to audition and sign her in-person. A young Sean "Puffy" Combs started in Uptown's mailroom and quickly moved to head of A&R as the mentee of Harrell. New jack swing music, the brainchild of Teddy Riley (of Guy) was basically housed at Uptown and the late Prince Markie Dee of the Fat Boys was a writer and producer for the label. In 1994, Harrell partnered with Law & Order creator Dick Wolf and delivered the hit series New York Undercover; which was an urban crime drama that regularly featured the hottest new Hip-Hop and R&B artists performing on the show.

Decades before the term "Black Excellence" became popular, Andre Harrell was insistent on pushing just that. "My goal is to bring real black America, just as it is not watered down to people everywhere through music, films and everything we do," he told Vanity Fair in 1993. He described Uptown as a lifestyle and he described what he sees as four categories of the Black audience. The first he explained “Are ghetto niggas, who come from poverty stricken environments and have the minimum society has to offer. Ghetto niggas have a natural sense of edge. Then there are lower-middle-class Black people, who conform to what they think white people like in order to get ahead. You call these people 'colored folks.' Then you have people who are on the upper echelons of the Black community. They are second-generation, educated, suburban, upper-middle-class—probably elitist—intellectual negroes. And then the best of all these situations, from ghetto to color to elitist intellectuals, is to be Black—when you can be who you truly are in any situation and feel good about yourself. If you don’t feel like you have to conform in your dress or your attitudes, you become a Black person. You cross all boundaries.”

“And that is the idea behind Uptown. It’s a lifestyle.”

Harrell became CEO of Motown Records in the mid-1990s where he stayed until 1998. In 2002, he discovered and mentored Robin Thicke, who would later become a powerful force in R&B. He would later work with Puffy as Bad Boy Records President and Vice-Chairman of Revolt TV.