Henderson was once a director of field operations at CTU, until Jack Bauer, whom he was a mentor and supervisor to, discovered he was selling classified intelligence to defense contractors, and Henderson was fired. He claimed he was set up by Nina Myers or George Mason.
Henderson was hired by Charles Logan and Graem Bauer to help them with their conspiracy to sell nerve gas to terrorists, led by Vladimir Bierko, to send a message that the US has weapons of mass destruction. David Palmer found out about this plan, so Henderson and Graem gave Conrad Haas the order to assassinate him. Haas also killed Michelle Dessler and tried to kill Tony Almeida and Chloe O'Brian to frame Jack, although the framing was quite unsuccessful, and Jack killed Haas.
While investigating Bierko, Jack was led to Henderson, who claimed to not know anything about the conspiracy, and then tried to kill Jack with a bomb, although Jack was able to survive. Henderson returned home, but Jack arrived there as well and threatened to kill his wife Miriam if Henderson didn't give him information on the nerve gas. Henderson refused to talk, willing to let his wife die for the conspiracy.
Henderson was taken to CTU and interrogated, Burke torturing him with hyoscine-pentothal. Tony wanted revenge on Henderson for killing Michelle, and planned to kill him with an overdose of hyoscine-pentothal, but could not bring himself to do so while he was unconscious and helpless. Henderson suddenly opened his eyes and stabbed Tony with the needle, killing him (temporarily) and escaping.
When Wayne Palmer was on his way to receive information about his brother's death, Henderson tried to have him killed, but failed. Evelyn Martin was the one who had the information, so to prevent her from talking, Henderson kidnapped her daughter, Amy. After Jack and Wayne rescued Amy, Evelyn told them of Logan's involvement in the conspiracy, giving Jack a recording. Henderson found out where Jack was going to be by threatening Evelyn and Amy, whom he possibly killed afterwards.
Jack gave the recording to James Heller to give to the attorney general, but he instead decided to use it to force Logan to step down quietly. This failed, as Henderson captured Jack and Audrey Raines and took the recording by cutting an artery in Audrey's arm, which threatened to kill her unless Jack gave over the recording. Henderson kept the recording for himself to prevent Logan from killing him for any reason like he killed Walt Cummings.
Although Jack was able to get Henderson into custody, he threatened to have one of his men in a helicopter kill Heller if Henderson was unable to contact him every 15 minutes. Realizing this, Heller crashed his car over a cliff into the water (although he survived). Audrey wanted to kill Henderson for her father's supposed death, but like Tony she couldn't go through with it. Henderson's men arrived, but were killed by Curtis Manning, and Henderson was taken to CTU.
When Bierko was in the process of launching a Russian submarine's missiles, Jack and Henderson teamed up to stop him, Henderson doing this in exchange for immunity, as well as disappearing so as to avoid being killed by Graem. Henderson took part in a sting operation to get information on the submarine from an illegal arms dealer, Joseph Malina. He told Malina that CTU were out there, seemingly doublecrossing them, but his true intention was to get Malina to put all his information on a flash drive.
Jack and Henderson found the submarine, the Natalia, and Henderson stopped the missiles from launching while Jack killed Bierko. Jack never intended to let Henderson go, however, unable to forgive him for killing David Palmer, Michelle, and Tony. Henderson knew Jack would try to kill him so he tried to shoot him with the gun Jack gave him, which turned out not to be loaded. Jack shot him in the chest twice, killing him.
- Christopher Henderson's death is similar to that of Victor Drazen; Both are killed at the harbor at nighttime, shoot at Jack with an unloaded weapon, and are executed by Jack in revenge for killing someone close to him.
- The theme that plays when Christopher Henderson gets into his car in his first episode is the same as part of Mandy's theme in Season 4 of 24 (called Mandy's Plan on the CD).