In the latter half of 2015, Roman Reigns, Dean Ambrose and The Usos occasionally formed a team when Reigns and Ambrose were outnumbered during their feud with The Wyatt Family in September 2015, Jimmy Uso (acknowledging familial ties) allied with Reigns and Ambrose in a match against The New Day, but said match was interrupted by The Wyatt Family attacking Jimmy. On the November 2, 2015 episode of Raw, Jey Uso returned from a legitimate injury (after six months out) as The Usos joined Reigns' team (with Ambrose and Ryback) in a five-on-five traditional Survivor Series match; Reigns and Ambrose survived the match, but both Usos were eliminated. In late November to early December 2015, The Usos teamed together with Reigns and Ambrose in several multi-man matches against The League of Nations group and other opponents.

In April 2016, AJ Styles earned a title shot for the WWE World Heavyweight Championship against champion Roman Reigns, while the debuting Karl Anderson and the returning Luke Gallows attacked The Usos on their first week together on Raw, and assaulted Reigns on their second week on Raw.

On the April 25 episode of Raw, Reigns and The Usos agreed to an alliance, and Reigns single-handedly saved them from a post-match attack by Anderson and Gallows. Later on the same episode, Styles agreed to ally with Anderson and Gallows if they fought fairly, but When Anderson and Gallows conducted another post-match attack on Reigns, Styles saved Reigns, who attacked him in response as Reigns was laid out when Styles retaliated. At Payback, Anderson and Gallows interfered in the (restarted) no disqualification Reigns-Styles world title match, which caused The Usos to arrive to brawl with them and, after Reigns twice attacked the four interfering men, he pinned Styles to retain his championship.

This led to a feud between the trio of Anderson, Gallows and Styles and the trio of Reigns and The Usos; after Styles' trio beat Reigns' trio on the May 2 episode of Raw, Anderson and Gallows wanted Styles to hit Reigns with a chair, but Styles refused, resulting in The Usos attacking Styles from behind with a chair, and Styles retaliating with the chair. Ultimately, Reigns established his dominance by hitting a powerbomb on Styles through the announce table. On the same week's SmackDown, the two trios had a rematch where Reigns pinned Anderson. On the next week's Raw, Reigns and The Usos defeated The Club (Anderson, Gallows and Styles) in a six-man elimination tag team match: Jey Uso, then Anderson, Jimmy Uso, and Gallows were pinned, and finally Styles was disqualified when Anderson interfered to prevent Reigns repeating his announce table powerbomb on Styles. On the May 12 episode of SmackDown, The Usos defeated Anderson and Gallows via disqualification, but Anderson and Gallows came up top in the post-match brawl with neither Reigns nor Styles appearing to help. On May 16, 2016, WWE christened the trio of Reigns and The Usos as "The Bloodline"; while on Raw that day, The Usos defeated Anderson and Gallows via pinfall.

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