Raised in Wollongong, Brendan played his junior football with Wollongong Wolves.
The forward signed his first senior contract with Parramatta Power in the National Soccer League and also played for Sydney United before heading overseas to join Geyland United (Singapore), Oostende (Belgium), St Truiden (Belgium) and Ujpest (Hungary).
The Croatian-Australian returned home in 2007 when he joined Sydney FC for two seasons and won the Hyundai A-League 2007-08 Goal of the Season for a brilliant strike against Adelaide United. Despite signing with North Queensland Fury in their debut year Brendon never played a match for the expansion club as he was picked up by Chinese club Chendu with Fury granting his release.
Brendon then played a season for fellow Chinese club Chongqing Lifan before being announced as a Wanderer on 6 August 2013.
He made his debut in Round One of the Hyundai A-League 2013/14 season and scored his first Wanderers goal against Brisbane Roar in Round Seven. Brendon wrote himself into Wanderers history when he became the Red & Black's first ever goal scorer in the AFC Champions League when he struck 40 seconds into the Club's debut against Ulsan Hyundai.
After a brave performance in the Champions League Final where he played with a broken collarbone, Brendon had a very disruptive 12 months with injury before finding some consistent gametime in the 2015/16 season. The popular striker played his 50th match for the Wanderers against Adelaide United in Round 13 of that year.
2015/16 saw Brendon mould into an effective super-sub, a role he flourished in when he scored in three consecutive matches for the first time in his career - all off the bench. In fact, his first 11 appearances of the season saw nine wins, two draws and zero losses. His consistent form earned him a two year contract extension that he signed on 10 February 2016 as he went on to claim his first Golden Boot award with 11 goals to equal the club's highest ever tally for a season.
Santalab went on to beat his season best in 2016/17, claiming his second consecutive Golden Boot award after scoring a Club-high of 14 goals in the Hyundai A-League. He also joined the list of Wanderers players to have scored a hat-trick and is now the Wanderers highest goal scorer of all time, scoring 37 goals during his tenure.
For the first tiime Santalab was named Player of the Year, voted by his fellow teammates, capping off what would be another history-making season for the striker.