Born in Callaway County, Missouri, Joseph Isaac "Ike" Clanton was one of seven children of Newman Haynes Clanton, (1816–1881) and his wife Mariah Sexton (Kelso) Clanton. His father worked at times as a day laborer, a gold miner, a farmer, and by the late 1870s, a cattleman in Arizona Territory.

Clanton's mother died in 1866. Ike stayed with the family when they moved to Tombstone, Arizona Territory, about 1877 (before Tombstone became a town or even a mining center). At that time, Newman Clanton was living with his sons Phin (or "Fin"), Ike, and Billy. By 1878 Ike was running a small "lunch counter" at the Tombstone Mill site (now Millville on the San Pedro River—not in modern Tombstone). By 1881, however, he was working on his father's ranch at Lewis Springs, about 12 miles (19 km) west of Tombstone and 5 miles (8.0 km) from Charleston.

In November 1879, shortly after arriving in Tombstone, Earp had a horse stolen. More than a year later, probably sometime in December 1880, Earp was told the horse was being used near Charleston, and Wyatt and Holliday were forced to ride to the Clanton's ranch near Charleston to await ownership papers in order to legally recover it. According to Wyatt's testimony later, 18-year-old Billy Clanton asked him insolently if he had any more horses to "lose," but he gave the horse up without first being shown the ownership papers, demonstrating to Wyatt that Billy Clanton knew to whom the horse belonged. Sheriff Johnny Behan later testified that the incident had angered Ike Clanton. It also angered Earp.

Clanton was later accused, along with his brother, Phin Clanton, and friend Pony Diehl, of attempting to kill Virgil Earp on December 30, 1881, a shooting which left Virgil with a crippled left arm. Though Ike Clanton's hat was found at the scene where the ambushers waited, a number of associates stood up for him, saying that he had been in Contention that night, and the case was dismissed for lack of evidence.

Deputy U.S. Marshal Wyatt Earp led a federal posse that escorted Virgil Earp to the railroad, bound for his parent's home in Colton, California. Wyatt shot and killed Frank Stilwell, who was lying in wait at the Tucson, Arizona rail yard. A few days later Wyatt gathered a larger posse and set out on a vendetta, determined to mete out justice that had evaded him. Wyatt never located Clanton, although they killed three other outlaw Cowboys, and the Earps and Holliday left the Arizona Territory in late April, 1882.

A reporter who corresponded with Brighton in late June 1887 relayed Brighton's story about the arrest and shooting:

Clanton is portrayed by Grant Withers in the John Ford classic My Darling Clementine (1946). Lyle Bettger portrayed Clanton as a brutal thug in John Sturges' film Gunfight at the O.K. Corral (1957). In Sturges' sequel, Hour of the Gun (1967), he is portrayed very differently as a highly sophisticated figure by Robert Ryan. Although the film is a generally accurate depiction of the events surrounding the gunfight at OK Corral and the subsequent Earp Vendetta, it errs in showing Clanton as having been tracked down in Mexico and shot by Wyatt. Later films correctly show Wyatt allowing Clanton to live. Clanton appears in the Doctor Who story "The Gunfighters" (1966), played by william Hurndell, which is largely based on the Sturges film and portrays Ike as the villain, albeit a somewhat comedic and inept one. It differs from history by showing Clanton participate and die in the OK Corral gunfight.

In 1957, Kelo Henderson played Clanton in an episode of Dale Robertson's NBC series, Tales of Wells Fargo.

From 1959 to 1960, the actor John Milford portrayed Clanton in eight episodes of the ABC/Desilu television series, The Life and Legend of Wyatt Earp, starring Hugh O'Brian in the title role. Trevor Bardette played Ike's father, Newman Haynes Clanton, known as Old Man Clanton. The role of Clanton was played by william Tannen in the episode "After the OK Corral" of the syndicated western anthology series, Death Valley Days. Jim Davis played Wyatt Earp in this same episode of Death Valley Days. Tannen had earlier played the role of Deputy Hal Norton on The Life and Legend of Wyatt Earp.

In the original Star Trek series episode titled "Spectre of the Gun" (1969), Captain James T. Kirk (William Shatner) plays the part of Clanton throughout the episode as part of an alien illusion test. DeForest Kelley (Dr. Leonard McCoy) also played this character in an episode of the CBS television series You Are There prior to Star Trek. Coincidentally, Kelley also portrayed Morgan Earp in the 1957 John Sturges film, Gunfight at the O.K. Corral.

Stephen Lang played Clanton in the movie Tombstone (1993) starring Kurt Russell as Wyatt Earp. This film draws heavily on the book by former Tombstone Assistant Marshal Billy Breakenridge, Helldorado: Bringing the Law to the Mesquite. In the film, Clanton is portrayed as being second-in-command of the Clanton Gang and the plot's comic relief. Although he is sadistic and talks tough, he is cowardly, as he begs for his life whenever someone is trying to kill him.

Jeff Fahey played Clanton in the movie Wyatt Earp (1994) starring Kevin Costner as Wyatt Earp. Christopher Fulford played him in 2007 in the BBC drama-documentary Gunfight at the O.K. Corral.

In late June 1996 a Clanton family descendant, Terry “Ike” Clanton, along with former Citadel professor and grave expert James A. Browning, searched the area near Eagle Creek in what is now Greenlee County, Arizona, where Ike was reportedly buried. They quickly discovered a shallow grave under a large tree that they believe contains the remains of Ike Clanton. Since their discovery, Terry has unsuccessfully tried to interest Tombstone city officials in exhuming the remains and re-interring them in Tombstone’s famous Boot Hill graveyard. Ike was survived in death by many relatives whose descendants still occupy the southwest today, including Tyler Clanton, a health care executive from Lubbock, Texas.

Later in the morning, Clanton picked up his rifle and single-action revolver from the West End Corral, where he had stabled his wagon and team and deposited his weapons after entering town. By noon that day, Clanton, drinking again and armed, told others he was looking for Holliday or an Earp. At about 1:00 pm, Virgil and Morgan Earp surprised Clanton on 4th Street where Virgil pistol whipped him from behind. Disarming him, the Earps took Clanton to appear before Judge Wallace for violating the city's ordinance #9 against carrying firearms in the city. Virgil Earp went to find Judge Wallace so the court hearing could be held.."

Cochise County Sheriff Johnny Behan, a friend to the Cowboys, later testified that he first learned of the trouble while he was getting a shave at the barbershop after 1:30 pm, which is when he had risen after the late-night game. Behan stated he immediately went to locate the Cowboys. At about 2:30 pm he saw both Clantons and both McLaurys gathered off Fremont street in a narrow 15–20 feet (4.6–6.1 m) wide empty lot or alley immediately west of 312 Fremont Street, which contained Fly's 12-room boarding house and photography studio. The lot was six lots removed from the rear entrance to the O.K. Corral.

At about dawn on October 26, the card game broke up and Behan and Virgil Earp went home to bed. Clanton testified later that he saw Virgil take his six-shooter out of his lap and stick it in his pants when the game ended. Not having rented a room, McLaury and Clanton had no place to go. Shortly after 8:00 am barkeeper E. F. Boyle spoke to Clanton, who had been drinking all night, in front of the telegraph office. Boyle encouraged him to get some sleep, but Clanton insisted he would not go to bed. Boyle later testified he noticed Clanton was armed and covered his gun for him, recalling that Clanton told him "'As soon as the Earps and Doc Holliday showed themselves on the street, the ball would open—that they would have to fight'... I went down to Wyatt Earp's house and told him that Ike Clanton had threatened that when him and his brothers and Doc Holliday showed themselves on the street that the ball would open." Clanton said in his testimony afterward that he remembered neither meeting Boyle nor making any such statements that day.