Sewell was selected with the 6th pick overall in the 2003 Rookie Draft. He played his junior football at the Newlyn Football Club which is part of the Central Highlands Football League and later with the North Ballarat Rebels in the U18 TAC Cup competition.
2006 proved to be his breakout year, when he was third in the club's Best and Fairest, collecting 130 votes behind Sam Mitchell and Luke Hodge. He played all 22 games for the season, and kicked his first and second goal in the last match of the year against Geelong.
Sewell is seen as one of the AFL's best taggers as he is able to gather the ball and still play his own game while limiting someone else's. A key player for Hawthorn and was the 2007 Peter Crimmins Medalist, winning by one vote over runner-up Campbell Brown.
On Saturday, 27 September 2008, Sewell became a Premiership player, after the Hawks beat the reigning premiers Geelong in the Grand Final.
In the final round of 2009, Brad Sewell suffered a fractured cheekbone and eye socket when he was knocked out by a shirtfront from Essendon captain Matthew Lloyd at the start of the third quarter. This was the turning point in the match, as Hawthorn went on to lose the match and miss the finals after leading at the time of the incident. Lloyd later received a 6-week suspension (reduced to 4-weeks with guilty plea) for the hit, and he subsequently announced his retirement.