He made his debut during the 1995 season, and won a premiership the following year, during which he was also nominated for the AFL Rising Star award.

Another premiership followed in 1999, and in 2002, Simpson was named in the All-Australian team and also won North Melbourne's best and fairest award, the Syd Barker Medal.

He was appointed club captain in 2004, and held the position until stepping down at the end of the 2008 season, with his span including a preliminary final in 2007.

Simpson also had a stint in the East Gippsland town of Sale where he was part of an under 15's premiership under coach Vince Moro.

Simpson also played a key midfield role for North Melbourne when the team won the 1999 Grand Final.

That year he missed two games with a punctured lung, but he still tallied over 400 disposals for the season with his industrious playmaking style.

[4][5] Round 5, 2007, he racked up a career equalling high 41 disposals, including a goal, in the Roos 16 point win against Geelong at Kardinia Park.

Simpson, Daniel Pratt and five other North Melbourne players admitted to producing a YouTube video entitled "The Adventures of Little Boris".

[14][15][16] In his first year as senior coach, the Eagles under Simpson finished 9th at the end of the 2014 AFL season, just missing out of the finals.

The following year in the 2015 AFL season, Simpson and the Eagles surprised many commentators by their performance when the club finished 2nd at the end home & away rounds.

[19] After three consecutive years without making the finals, including one 'horror' season in 2023, where West Coast Eagles finished last on the ladder, on July 9th, 2024, in the middle of the 2024 season, after Round 17, 2024, with no improvement in on-field performance with the Eagles sitting at sixteenth (third-last) on the ladder, Simpson was sacked as senior coach of the West Coast Eagles in a mutual agreement with the club that Simpson's 11-year tenure as senior coach would come to an end, effective immediately.