Block was born in London. At the age of 4, he moved to Wembley along with his mother, who still lives there today. Block's career started out in 1985 at the John Lyon pub in Harrow, Middlesex. According to Block himself, "My friends and I used to buy a lot of funk and soul (the sound at the time) and one night the DJ there didn’t show, so me and my then DJ Lewis asked the governor if we could bring the records down and do it. We were so good that he fired the DJ. In fact, it got so popular that they started charging an entrance fee".
In 1988, he got his first club residency at ZigZag at the Broadway Boulevard in Ealing, west London. Whilst there, he met Dean Thatcher (best known as a founder member of techno/house act The Aloof) and started up his own night called Haven Stables, which ran until 1991. The previous year, he went to Ibiza for the first time with the record label he was working for at the time. During his time, he has also held residencies at Up Yer Ronson in Leeds, FUBAR at the Milk Bar in London, Club For Life in London, and Scream in Plymouth. He has also played numerous other venues such as the Ministry of Sound, Turnmills, Miss Moneypenny’s, Republica, Progress, Karanga and Colours. Several appearances on BBC Radio 1's Essential Mix show appeared, as did Muzik magazine awarding him the "Caner of the Year" prize three times.
In 1996, Block was experiencing problems in his private life. His love of partying and hedonistic lifestyle was taking its toll on his health. He had a cocaine addiction which was costing him up to £2,000 per week. This resulted in him missing numerous gigs he had been booked to play and Block got into debt. In 2009, Block agreed to take part in an anti-drugs campaign for the government. He revealed that he had picked up illnesses including a lung infection which meant a portion being removed and hepatitis and said that doctors had told him to give up drugs immediately – otherwise, he would have "two weeks to live". Speaking in 1997 about this, he said of detox: "It's been fucking hard. I'm nine months clean now – I still smoke cigarettes and I still have a bit of a booze, but I don't take any drugs at all. It's taken all this time for me to feel even remotely normal." Of the easy accessibility of drugs in the music industry, he said, "That’s the problem – it’s always there, but you have to make a decision. Make it and then there’s no going back – you can’t mess around with that stuff. The fact was that it was something I liked doing, it was good fun at the time, as well as being available and I had the money to do it. The more you take, the more you want – unfortunately that’s the way it is. Then you go down the slope".
During detox, he was forced to take six months off from the DJ circuit in 1996. As his health improved the following year, so did his fortunes. In October 1997, he became a radio presenter alongside his old friend Alex P, presenting a show on Kiss 100. Later, he had three singles released under his Blockster alias – "Something Goin' On", "Grooveline" and "You Should Be.." –, all of which were released by Ministry of Sound. "You Should Be..." was a remix of "You Should Be Dancing" by the Bee Gees, and reached number 3 in the UK Singles Chart in January 1999, and "Grooveline", which heavily sampled The Groove Line by Heatwave, reached number 18 in July 1999.
He is well known for appearing on stage heavily intoxicated at the 2000 BRIT Awards. Friends suggested that he had entered a musical contest and had won Best Musician of the Year, when in fact he had not even been nominated for the award. This resulted in a confrontation with award presenter Ronnie Wood and Thora Birch.
In 2005, he appeared on the chatshow Heads Up with Richard Herring to discuss his life, career, anti-semitism, and his love of poker.
In September 2006, Block was on Five's reality television show Trust Me - I'm A Holiday Rep. He formerly, between 2000 and 2001, presented Brandon Block's Video Hits on Rapture TV.
On 13 January 2007, Block appeared on The Weakest Link Music Extravaganza Edition. He was the second to be voted off.
Block also hosted a show alongside fellow DJ and friend Alex P on MTV Dance, where they toured Ibiza interviewing clubbers from around the island, and played the latest dance videos.
On 21 June 2012, Block featured as the entertainment for one of the guests on Channel 4's Come Dine with Me.
On 3 January 2017, Block entered the Celebrity Big Brother house. He voluntarily left the house on Day 10.