The Great Khali and Bobby Lashley were originally scheduled to compete in their respective matches against The Undertaker in the Punjabi Prison match and against Finlay for the WWE United States Championship, but they were both pulled from the event due to elevated enzymes in the liver that would possibly signify hepatitis.

Mark Henry was also scheduled to compete against the returning Batista in a grudge match, however he ruptured his patellar tendon and dislocated his kneecap just before this event in a match on Saturday Night's Main Event XXXIII, forcing a replacement in the form of Mr. Kennedy.

[1] The main feud heading into The Great American Bash was between Rey Mysterio and King Booker over the World Championship.

On the July 7 episode of SmackDown!, Booker became the number one contender to the World Championship by last eliminating William Regal and Matt Hardy in a Battle Royal.

[10][11] One month later, on the edition of June 30 of SmackDown!, Khali challenged Undertaker to a Punjabi Prison match at The Great American Bash.

The first match of the event was Paul London and Brian Kendrick facing The Pit Bulls (Jamie Noble and Kid Kash) for the WWE Tag Team Championship.

Kendrick pinned Noble with a sunset flip with a dropsault from London to win the match and retain the title.

The third match was Gregory Helms versus Matt Hardy, who was substituting for Super Crazy, who was also suffering from elevated enzymes in his liver.

On-screen, General Manager Theodore Long put Big Show in the match instead of The Great Khali for attacking The Undertaker backstage.

In reality, Khali was not medically cleared to compete as, like Lashley and Super Crazy, he had elevated levels of enzymes in his liver.

The main event saw Rey Mysterio defend the World Championship against King Booker.

Following The Great American Bash, a rematch between King Booker and Rey Mysterio for the World Heavyweight Championship took place.

The match saw King Booker retain the World Heavyweight Championship, after interference from Chavo Guerrero.

Batista informed Cole to save his congratulations until after he won back the World Heavyweight Championship.

[16] The following week, Batista thanked King Booker for holding onto "his" World Heavyweight Championship and told him he would be needing it back at SummerSlam.

[17][18] At SummerSlam, Batista defeated King Booker by disqualification after Queen Sharmell interfered.

[23] A rivalry between Matt Hardy and Gregory Helms began after facing off at the Great American Bash.

The 2006 Great American Bash would be the final to be SmackDown!-exclusive, as following WrestleMania 23 in April 2007, WWE discontinued brand-exclusive PPVs.