[1] In July 2021, Hawthorn appointed Mitchell as the next senior coach, taking over from Alastair Clarkson at the end of the 2021 season.

After a couple of games in the reserves he gained promotion to the seniors and completed the season as the team's number one rover.

[14] On Saturday, 27 September, Mitchell captained the Hawks to the 2008 premiership, the first in 17 years and the club's 10th, beating the reigning premiers, Geelong, by 26 points.

[15] At the end of the 2010 season he handed the captaincy over to Luke Hodge, who was made captain of the 2010 All-Australian team.

[19][20][21] Mitchell was rewarded with the Peter Crimmins Medal in 2011, 2012 and 2016, and became a five-time best and fairest winner at Hawthorn, behind only Leigh Matthews, who won eight during his career.

[22][23][24][25] Mitchell became a triple premiership player with the Hawks in season 2014, and like a swathe of his teammates his year was interrupted by a serious injury.

Still averaging over 28 disposals per game for the season mixing between midfield and half-back, Mitchell played a critical role in Hawthorn’s back-to-back premierships and was recognised as such by being named the side’s best player in the finals series by his coaches.

[34] Sam Mitchell played the final game of his career in the semi-final, where he recorded two goals and twenty-eight disposals in a 67-point loss to Greater Western Sydney.

[39][40] On 6 July 2021, the Hawthorn Football Club announced that as part of a succession plan, Mitchell would succeed Alastair Clarkson as the senior coach of Hawthorn from 2023; until then, Mitchell will continue as Head of Development and as Box Hill Hawks senior coach.

[41][42][43] However, on 30 July 2021, it was announced that Clarkson would leave Hawthorn at the conclusion of the 2021 AFL season, with Mitchell immediately succeeding him.

[48] In the 2023 season, the Hawks under Mitchell finished sixteenth (third-last) position on the ladder with seven wins and sixteen losses and therefore not making finals.

[50] On 13 July 2015, Mitchell was found guilty by the AFL's match review panel of having kneed the right thigh of Fremantle Dockers player Nathan Fyfe during the second quarter of the previous day's game and was fined $1000 for the offence.

[53] Media reports from 2008 show that an opposition club, Brisbane, expressed concerns to the AFL about Sam Mitchell's kneeing of opponents.