Adesanya, 31, entered UFC 259 on the cusp of becoming just the fifth UFC star to hold titles in simultaneous weight classes, with the Last Stylebender favourite to see off light heavyweight champion Blachowicz.
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The judges scored the bout 49-46, 49-45 and 49-45, all for Blachowicz.
The match was decided in the early hours of Sunday.
The Nigerian steps into the octagon against Jan Blachowicz, the light-heavyweight title-holder, in a bid to add to his middleweight championship honours.
Adesanya, who boasts a 20-0 UFC record, is the reigning middleweight champion after defending his title against Paulo Costa in September, but is now moving up to light heavyweight.