UFC 181 was the organization's 300th event and was expected to be headlined by a Middleweight Championship bout between the current champion Chris Weidman and top contender Vitor Belfort. However, on September 22, it was announced that Weidman had suffered a broken hand and the bout was again rescheduled to take place at UFC 184. The new main event was a Welterweight championship rematch between champion Johny Hendricks and number one contender Robbie Lawler. Their first fight at UFC 171 ended in a unanimous decision victory in favor of the reigning champion.
Gian Villante was expected to face Corey Anderson at the event. However, Villante pulled out of the fight citing an injury and was replaced by Jonathan Wilson. A few days later, it was announced that Wilson was forced out of the fight and undefeated newcomer Justin Jones took his place.
During the PPV broadcast, it was announced that former professional wrestler and WWE championCM Punk had signed a multi-fight deal and was expected to debut in 2015, but after an injury ultimately debuted in September 2016.
A month subsequent to the event, on January 7, 2015, it was revealed that Ashlee Evans-Smith had failed her post-fight drug test, testing positive for a diuretic. On February 17, the Nevada State Athletic Commission ultimately decided to issue a nine-month suspension and fined her 30 percent of her purse ($2,400). She also needs to submit a clean drug test before her next fight.
The following fighters were awarded $50,000 bonuses:
Fight of the Night: Sergio Pettis vs. Matt Hobar
Performance of the Night: Anthony Pettis and Josh Samman
The following is the reported payout to the fighters as reported to the Nevada State Athletic Commission. It does not include sponsor money and also does not include the UFC's traditional "fight night" bonuses.