Beginning his career at Port Adelaide in 2000, he was seen as a potentially dangerous winger or forward. Brent Guerra also won three SANFL Premierships with Central District. However, at the end of 2003 he was traded from the club due to Guerra wanting to return to Victoria and the Saints picked him up for pick 39, who was the unsuccessful Robert Forster-Knight.
Guerra was a key figure for a period during the Saints' early season run in 2004 when St Kilda won the 2004 Wizard Home Loans Cup and the first 10 games of the home and away season. He kicked 20 goals in six games, including seven in one game. From then, however, his form tapered and he finished with only nine more goals from the remaining 12 games. He was noted for a number of incidents when he shirtfronted players, including once before the opening bounce of a game (for which he was suspended).
In 2005, Guerra had another average year and, at the end of the season, the Saints delisted him.
The Hawthorn Football Club selected Guerra with pick three in the 2005 AFL Pre-season draft. Guerra had a connection with Hawks' coach Alastair Clarkson from Clarkson's time as a premiership coach at Central Districts (2001) and assistant coach at Port Adelaide. Guerra was reinvented at Hawthorn as a strong-bodied half back flanker and added experience to a very young Hawks' lineup in 2006. His hard-nosed approach has at times attracted the attention of umpires. In 2007 and 2008 he averaged in excess of 20 possessions per game, displaying a consistency which was lacking earlier in his career up forward.
As a part of Hawthorn's 2008 premiership side, Guerra had 25 possessions in a reliable display.
In Round 23, 2012, a week before the finals with Hawthorn sitting on top of the ladder, Guerra sustained a hamstring injury. It occurred in the final quarter of Hawthorn's 25-point victory over West Coast. On 24 September, Guerra ruled himself out of the 2012 Grand Final against the Sydney Swans.
On 2 October 2013, the week following his second premiership with the Hawthorn Football Club, Guerra officially announced his retirement from AFL football to pursue a career in coaching.
Through Guerra's career he suffered from a recurring hamstring injury which kept him from playing in the 2012 Grand Final.
Guerra currently played for Deer Park in the Western Region Football League, having joined them on October 29, 2013. He won a premiership with Deer Park in October 2014.
Guerra also made a guest stint in three games for Devonport in the Tasmanian Football League in 2014.
In his final year as a player, Guerra completed a Level 2 coaching accreditation course and a diploma of management. Shortly after retiring from playing, Guerra was appointed a part-time development coach at the Hawks in November 2013.
On 19 September 2014, Guerra joined Chelsea in the Mornington Peninsula Nepean Football League as player-coach. Prior to the 2016 season, he was appointed as a development coach with Fremantle.
Guerra experienced male pattern balding at a young age and made headlines in late 2005 when he underwent a hair transplant cosmetic surgery procedure. He has said that the operation gave him confidence both on and off the field.
Guerra has a brother, Luke, who currently plays with Deer Park in the Western Region Football League.
Since retirement Guerra has revealed his struggle with gambling addiction whilst he was a professional footballer.