He played college football for the Colorado Buffaloes, the Saddleback Bobcats, and most notably with the Hawaii Rainbow Warriors, where he was a two-time third-team All-American before being selected by the Washington Redskins of the National Football League (NFL) in the sixth round of the 2008 NFL draft.

[1] After graduating from Mater Dei, Brennan attended Worcester Academy in Massachusetts for a postgraduate year, where his primary receiver was David Ball, who later would break Jerry Rice's college record for touchdown receptions in Division I-AA.

[4] Brennan, who was intoxicated at the time of the incident, was arrested and eventually convicted of charges of felony burglary and trespassing[5] (serving one week in jail along with probation until he graduated from college), but a guilty verdict for unlawful sexual contact was vacated by the court for lack of evidence.

He was named honorable mention JUCO All-American, state offensive player of the year by the JuCal Transfer, and first-team all-conference for his performance in that season.

He repaired his image well enough for the University of Hawaii head coach June Jones to offer him a walk-on opportunity.

[1] Brennan transferred to University of Hawaiʻi at Mānoa (Hawaii) in 2005 and quickly earned the starting quarterback job.

[7] Brennan entered 2006 as the undisputed starter at quarterback, was named to multiple award watch lists and was voted the WAC's preseason Offensive Player of the Year.

[2] Brennan finished 6th in the voting for the 2006 Heisman Trophy, behind Troy Smith, Darren McFadden, Brady Quinn, Steve Slaton, and Mike Hart.

[10] During the season, Brennan passed for 5,549 yards and 58 touchdowns, both of which are school records, and had the highest passer efficiency rating in the nation.

He threw the record-breaking 122nd in the first quarter, a six-yard touchdown pass to Ryan Grice-Mullen to surpass the mark set by former BYU quarterback Ty Detmer in 1991.

[19] Brennan was selected for the second year in a row as a Heisman trophy finalist, this time finishing in third place behind Tim Tebow and Darren McFadden.

[20] At the end of the season, he was invited to participate in the 2008 Senior Bowl, where he suffered a torn labrum in his right hip during the first day of practice.

[21] June Jones, Brennan's coach at Hawaii, had a large impact upon his career and helped him become one of the most prolific passers in NCAA Division 1 history.

Brennan was placed on injured reserve on September 4, 2009, thus ending his 2009 season, due to a torn hamstring and a hip injury.

[37] On August 2, 2010, the Redskins traded for Baltimore Ravens quarterback John Beck, thus making Brennan expendable.

[44] Although he was expected to be the backup, the Roughriders later signed former NFL journeyman J. T. O'Sullivan, pushing Brennan down in the depth chart.

On November 19, 2010, Brennan was hospitalized and listed in serious condition after he was a passenger in a car crash in the Big Island of Hawai'i.

[55] The crash left him with a traumatic brain injury, broken ribs and collar bone, which according to his family affected him emotionally in the following years.

[56][57] He was released from Queen's Medical Center on November 27, 2010, and headed to his parents' home in Southern California to continue his recovery.

I've had to learn how to control that.Brennan was arrested on July 25, 2012, in Kailua, Honolulu County, Hawaii, on suspicion of driving under the influence and third-degree promotion of a dangerous drug.

[63] In 2015, Brennan allegedly filed a false police report that his vehicle was stolen, something his attorney blamed on memory problems stemming from his 2010 car crash injuries.

The judge granted his lawyer's request for court-supervised release without bail until his next scheduled court appearance later that month.

[68][69] In addition, there were multiple substances in his system, including ethanol, methamphetamines, amphetamines, and fentanyl in the autopsy report.