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Brendon Santalab played his football with Wollongong Wolves Football Club (Youth League) in 1999 where he was honoured with Highest goal Scorer Award. Wollongong Wolves now known as Wollongong FC is is an Australian association football club based in the Illawarra region in New South Wales, Australia and a member of the former National Soccer League (NSL) until that league ended in 2004. They now play in the New South Wales Premier League. The Wolves won the OFC Champions League in 2001 and becoume NSL Champions in 2000 and 2001. In 2007 they won the Tiger Turf cup.

Brendon started his professional career with the Parramatta Power at the age of 17 years old, making him the youngest player to play in NSL at the time. Parramatta Power Soccer Club is a team which was based in western Sydney. They played in the National Soccer League from season 1999/2000 until the league folded in 2004. They were runners up to Perth Glory in the 2003/2004 season of the NSL. The club has since folded due to financial difficulties. The club was backed by the Parramatta Leagues club which also owns the Parramatta Eels rugby league team. The club played at Parramatta Stadium, the home of the Eels. The club suffered from poor attendances throughout its existence, partly because of its links to the Eels, as well as it's being in the already crowded western Sydney soccer market.

After playing two seasons with Parramatta Power Brendon and his brother Michael both moved to Sydney United. Sydney United Football Club is an Australian football club from Sydney established in 1957 by Croatian immigrants in the area. The club was formed as Sydney Croatia, but in 1993 was renamed Sydney United. The club played their home games at Edensor Park in Sydney's western suburbs.

During the Sydney Uniteds off season in 2003, Brendon was loaned out to Geylang United, in Singapore. Geylang United Football Club is a professional football club, currently playing in the S.League. The club is based in Bedok and their home ground is Bedok Stadium. The club was founded initially under the name International Contract Specialists in 1973. It changed its name to Geylang International in 1975, and then to Geylang United in 1996. The club set a Singapore Football record by winning 6 Premier League titles in a row between 1988 and 1993. The league and Singapore Cup double was also achieved in both 1990 and 1991. In 2003 they were Runners-up in Singapore Cup thanks to Brendons spectacular spell in the S.League. While at Bedok Stadium, Santalab scored 23 goals in only 22 appearances.
Brendon was nominated for SembCorp Power & Gas Young Player of the Year and one of his Goals was nominated for Tiger Beer Goal of the Year - "Geylang United FC vs Balestier Khalsa FC".

After a very succsesful stint in Singapore Brendon returned back to Sydney United. In 2004-2005 he went to the Belgian side KV Oostende. Koninklijke Voetbalclub Oostende is a Belgian football club, based on the coast. The club was created in 1904 as V.G. Oostende. In 1981 the club merged into A.S. Oostende and become K.V. Oostende. The team plays at Albertparkstadion.

After his KV Oostende period Brendon's trainer Herman Vermeulen was appointed trainer of a Belgian Premier League Koninklijke Sint-Truidense Voetbal Vereniging and he took Santalab with him to a new club. Sint-Truiden, KSTVV, is a Belgian football club located in the province of Limburg. The club was created in 1924 following the merger between F.C. Union and F.C. Goldstar, two local clubs. While at KSTVV, Brendon went through very difficult period due to injuries, change in coaching staff and he appeared in only 9 first Grade football games.

KSTVV who worked in a partnership with the Hungarian side Ujpest FC send Brendon on loan to Hungary for the second half of his second season with the club. Újpest Football Club, earlier known as Újpesti TE and Újpesti Dózsa, is a club, based in Budapest and playing in the Szusza Ferenc Stadium. Their 20 league titles and 8 cup titles make them one of the most successful clubs in Hungary. Brendon, who was still in rehab was loaned out to Ujpesti. After recovering from injury and training with Ujpesti he had another mishap at training and he sustained another injury. There were also a few problems with international transfer dates, therefore he was not registered to play until January 2007, when the transfer window opened again. He decided to return to Australia, attend to his injury and pursue and resurrect his football career, signing with Sydney Football Club (SFC) in the Hyundai A- League competition for 2007-2008 and 2008-2009 season.

After his European adventures, Brendon started 2007-2008 season with Sydney Football Club. Sydney FC was founded in 2004 and the team play their home games in the A-League at the Sydney Football Stadium. The club won the inaugural
A-League Championship in 2005–2006. In 2005 the team also won the Oceania Club Championship Cup. Brendon, is still under contract with Sydney FC for 2008-2009 season.

On 14 November 2008, it was announced that Santalab had signed a two-year contract with new A-League side the North Queensland Fury for the inaugural season, 2009–10. North Queensland Fury Football Club is an Australian professional association football (soccer) club based in Townsville, Queensland, and competes in the A-League.

Brendon Santalab signs with Chinese Super League outfit Chengdu Blades. Santalab signed a two-year deal with the Blades on 21/07/2009 after having his contract at Fury mutually terminated. Brendon joined the Fury from Sydney FC in November last season but was allowed to leave the fledgling club before appearing in a competitive match. Chengdu Blades F.C. are a football team from Chengdu, PR China who are owned by Sheffield United. They play in the Chinese Super League. This club was formerly known as Chengdu Wuniu (Five Bulls).