Selected in the third round of the 1994 National Draft, O'Loughlin played 12 senior games for the Swans in 1995 and earned a AFL Rising Star award nomination. The following year, he was a key player in the team that won the minor premiership and then lost to North Melbourne in the grand final. He was the games record holder for the Swans, passing John Rantall's record in Round 14 of the 2007 season, until he was overtaken by his close friend Adam Goodes. He became the first Sydney Swans/South Melbourne player to break the 300 games milestone in Round 19, 2009.
O'Loughlin played the majority of his early football in a half-forward flanker role, where his combination of speed, strength and agility made him a difficult player for opposing teams to match up against. He was known by the nickname "Magic" throughout his career, in recognition of his capacity to play football so skillfully that it could sometimes seem he had "cast a spell" on his opponents. He was also known by the nickname, "Micky O". In the latter part of his career, he was primarily used as Sydney's full-forward. In 2000 and 2001, he was the club's leading goalkicker. He was club best and fairest in 1998 and runner-up in 2000. He was selected in the All Australian Team in 1997 and 2000. When State of Origin matches were still being played, he represented his state on several occasions, receiving the Fos Williams Medal for best South Australian player in 1998.
O'Loughlin, the only player remaining in the team from the 1996 loss, played strongly during the 2005 grand final, including a number of exceptional marks. However, and uncharacteristically, his kicking for goal during the game was inaccurate.
In 2006, O'Loughlin continued to be a key part of the Swans' line-up, including playing a decisive role in the qualifying and preliminary finals that put the Swans into the grand final for the second consecutive year. In the 2006 Grand Final, O'Loughlin played well, kicking 3.1 (19). He continued to play consistently well for Sydney through the balance of his career.
In the close 2006 Qualifying Final against the West Coast Eagles at Subiaco Oval, O'Loughlin ran into an open goal, then carried on to the fence and roared into the faces of some rather stunned-looking Eagles' fans from a few inches away. The moment is captured in Jamie Cooper's painting the Game That Made Australia, commissioned by the AFL in 2008 to celebrate the 150th anniversary of the sport.
On 23 June 2009, O'Loughlin announced that at the end of the 2009 season he would retire. He played his 300th game in round 19 at the MCG against the Richmond Tigers.
Since leaving the AFL, O'Loughlin has continued a media profile. In September 2009 he launched the Goodes O'Loughlin Foundation (www.go-foundation.org), along with his cousin & co-Chairman Adam Goodes, focused on Education, Employment, and healthy Lifestyles. The Foundation's mission is to develop and empower the next generation of Indigenous role models in Australia.
O'Loughlin was awarded the 2009 AFL Players’ Association Madden for his on and off-field contributions to the game.
In 2000, it was alleged that O'Loughlin had participated in the rape of a woman in a park in Adelaide along with two other AFL players, Adam Heuskes and Peter Burgoyne. The woman claimed that while Heuskes and Burgoyne raped her, O'Loughlin masturbated close to her face. O'Loughlin was neither charged nor questioned by police but Burgoyne and Heuskes were both charged with rape. The case, however, did not go to court as the Director of Public Prosecutions, Paul Rofe, said there was "no reasonable prospect of conviction on any criminal charge" due to a lack of witnesses. Despite this, the three players made a $200,000 cash payment to the alleged victim. The incident came to public light when it was examined on the ABC investigative program Four Corners in 2004.
^Micky O: Hard Work. Determination. And a Little Bit of Magic, Jim Main, Michael O'Loughlin - 2012
^Michael O'Loughlin, Episode 6, Season 4, Who Do Think You Are?, SBS "his mother's maternal line, which stretches all the way back before white settlement and to his great, great, great, great grandmother, Kudnarto, a full blood Kaurna woman. Michael discovered that Kudnarto's husband and Michael's great great, great, great grandfather is in fact a white settler called Thomas Adams"