Born in Uccle, Axel Merckx became a professional cyclist in 1993, winning the Belgian national road race championship in 2000. He repeatedly vowed to make his mark by accomplishing feats that had eluded his father Eddy, such as winning a Tour de France stage at Alpe d’Huez and the Paris–Tours classic. He did not succeed, but competed in eight Tours de France and finished as the highest-placed Belgian rider six times. His personal best was cracking the top 10 during the 1998 edition.

Merckx married Canadian triathlete Jodi Cross in 1997, and currently resides in Kelowna, British Columbia. They have two children, Axana (born 5 May 2001) and Athina Grace (born 29 June 2005).

During the 2006 Tour de France, Merckx announced that he signed a new contract for one extra season with Phonak, later renamed iShares. He stated that this would be his last season as a professional road bicycle racer. However, after Phonak announced that it would stop sponsoring the cycling team, Merckx signed a contract with Team T-Mobile, where he had started his professional career. During the 2006 Tour Merckx was instrumental in forcing the pace of the peloton for teammate Floyd Landis who won the Tour. He was often times the only teammate able to stay with Landis and the group of favorites and he initially finished 31st overall, however it was later discovered that Landis had failed a doping control after stage 17 and the Tour win was revoked.

Merckx announced his retirement from professional cycling at the end of the 2007 Tour de France. He won his last race at Lommel, in August 2007.

He created the Granfondo Axel Merckx National Series, with its inaugural event being the Granfondo Axel Merckx Okanagan on 10 July 2011 in Penticton, British Columbia. His father, Eddy, rode in the inaugural event.

His name was on the list of doping tests published by the French Senate on 24 July 2013 that were collected during the 1998 Tour de France then retested in 2004. Merckx was not one of then 18 Riders named as testing positive for EPO but was on a list of 12 named riders whose test results were listed as “suspicious”.