The main rivalry heading into Night of Champions from the Rawbrand featured the defending champion Sheamus, Randy Orton, John Cena, Chris Jericho, Edge and Wade Barrett, feuding over the WWE Championship. At the Fatal 4-Waypay-per-view in June, Sheamus won the WWE Championship in a fatal four-way match, and at Money in the Bank in July, defeated Cena to retain the title in a Steel Cage match. At SummerSlam, Sheamus lost to Orton in a championship match via disqualification, but as per WWE rules, retained the title. On the televised August 23 episode of Raw, the "anonymous" general manager of the show set up a series of matches that night to determine the next contender for the WWE Championship, and allowed Sheamus himself to handpick his opponent for Night of Champions. The matches saw Edge defeat R-Truth, Jericho defeat The Great Khali, and Orton defeat John Morrison and Ted DiBiase in a Triple Threat match, while The Miz defeated Cena via disqualification. During the night, Barrett called off The Nexus' "truce" with Sheamus, and at the end of night decided to cash-in his right (due to winning the first season of WWE NXT) to challenge for the WWE Championship at Night of Champions. However, the general manager announced that Sheamus was to defend his WWE Championship against Orton, Cena, Jericho, Edge, and Barrett in a Six-Pack Challenge at Night of Champions. On the 900th episode of Raw, Chris Jericho added a stipulation that if he cannot win the championship, he will leave the WWE. However, the following week, he participated in a match with John Morrison under the stipulation that he would be taken out of the Night of Champions match if he did not win. Jericho lost the match and was removed from the Six-Pack Challenge. On the September 13 episode of Raw, the anonymous General Manager of Raw announced the match was changed to an elimination format. In addition, the General Manager also offered Chris Jericho an opportunity to re-insert himself in the match via a handicapsteel cage match against The Hart Dynasty. Jericho was successful in defeating the duo and thus was re-admitted to the Six-Pack Challenge.
The main rivalry from the SmackDown brand featured the champion Kane against his storyline half-brother The Undertaker for the World Heavyweight Championship. Approximately three months prior to the pay-per-view, The Undertaker had been mysteriously put in a vegetative state. Upon finding out about this, Kane had attempted to seek vengeance against the culprit. At the Money in the Bank pay-per-view, Kane had won the Money in the Bank ladder match and cashed in his briefcase later that night against then champion Rey Mysterio. Mysterio used his rematch clause on Kane to challenge him at SummerSlam but failed. During the weeks leading up to SummerSlam, Kane was convinced that Mysterio was the one behind the attack on his brother and upon defeating him, attempted to put him in a casket when The Undertaker appeared inside it. Upon seeing his brother again, Kane attacked The Undertaker turning him heel. On the September 3 episode of SmackDown, Kane challenged the Undertaker putting his Championship on the line and promises to end The Undertaker for good.
Another rivalry involved an inter-brand match involving the Divas ChampionMelina and the WWE Women's ChampionLayla and Michelle McCool, collectively known as Team Lay-Cool, in a Title Unification Match. On May 14, Layla had pinned then-Women's Champion Beth Phoenix in a two-on-one handicap match which awarded Layla the championship. However, both Layla and McCool decided to make themselves Co-Women's Champion (as, by their logic, the Championship was won in a handicap match), going as far as splitting the main championship belt to keep co-reign. At SummerSlam, Melina had won the Divas Championship from former champion Alicia Fox. After the match, Lay-Cool had attacked Melina, stating they had defeated everyone on the SmackDown brand while champions and decided to go after Raw Divas. On the 900th episode of Raw, Lay-Cool challenged Melina to a Title Unification match. Melina accepted under one condition, their match would be a Lumberjill match.
Another rivalry from Raw involved champion The Miz against Daniel Bryan for the WWE United States Championship. The feud had begun during the first season of NXT, when The Miz was Bryan's storyline mentor, and felt that Bryan did not respect him. Bryan had been released from WWE in June, but returned at SummerSlam to join Team WWE, taking The Miz's place. Afterward, the two resumed their rivalry, distracting or attacking each other during matches, with The Miz joined by his rookie from the second season of NXT, Alex Riley. On the September 6 episode of Raw, Bryan challenged The Miz for the United States Championship, which The Miz accepted.
Another SmackDown rivalry involved the champion Dolph Ziggler against Kofi Kingston for the WWE Intercontinental Championship. On the August 6 episode of SmackDown, Ziggler defeated Kingston for his Intercontinental Championship. Kingston got a rematch at SummerSlam only for The Nexus to interfere resulting in a no contest. Following this, Kingston got several rematches against Ziggler only to be disqualified for one of them and counted out for another. To correct this, General Manager Theodore Long declared that Ziggler would defend his title against Kingston and if he were to be disqualified or counted out, then the title would go to Kingston.
Writing for The Sun, Rob McNichol rated the event 8.5 out of ten. He praised most of the matches, especially the United States Championship match, Kane vs Undertaker, and the main event, which he described as "superbly booked".