Yes and no. The actual characters and the specific narrative events depicted in the film are completely fictional; Liz Hunter (Cassandra Magrath), Kristy Earl (Kestie Morassi) and Ben Mitchell (Nathan Phillips) were not real people, and what they experience in the film never happened in reality. However, the overall plot (tourists going missing in the outbreak due to their encounter with a killer) is loosely based on reality, specifically the cases of Ivan Milat (aka the Backpacker Murders) and Bradley John Murdoch (aka the Peter Falconio mystery).
Fans are generally in agreement that the main real life influence on the film was Ivan Milat, who killed at least 7 victims between 1989 and 1994 in New South Wales. On September 20, 1992 a decomposing body was discovered in the Belanglo State Forest, with a second body found nearby the next day. Police were quickly able to confirm that the bodies were those of British backpackers Caroline Clarke and Joanne Walters. Walters had been stabbed 9 times, and Clarke had been shot several times in the head and stabbed post mortem. Investigators looking into the case determined that it was a random incident, and the chances of finding any more bodies in the Forest was negligible. However, in October 1993, a man discovered a human skull and thigh bone in a remote section of the forest, and when the police examined the scene, they discovered two more bodies, which were subsequently identified as Victorian couple Deborah Everist and James Gibson. Then, on November 1, 1993 another skull was found in a clearing in the forest. The skull was later identified as that of Simone Schmidl from Germany, who had been last seen hitch hiking on January 20, 1991. Like Walters, Schmidl had been stabbed to death. Clothing found at the scene matched that of yet another missing backpacker, Anja Habschied. The bodies of Habschied and her boyfriend Gabor Neugebauer were then found on November 3, in shallow graves near the area where Schmidl's skull was found. Habschied had been decapitated. Because of the different methods of execution, it was felt that the murders were perhaps the work of two killers working together, one who stabbed his victims, one who shot them (in his subsequent trial, Milat claimed that there were actually seven killers in total).
The case broke on November 13, 1993, when police received a call from Paul Onions in Britain. Onions had been backpacking in Australia and had accepted a ride south out of Sydney from a man calling himself Bill. Near Mittagong, Bill's initially jovial manner had changed and he had pulled a gun on Onions, who managed to escape, flag down a passing car and flee. Around the same time, the girlfriend of a man who worked with Ivan Milat suggested that police talk to him about the murders.
Upon investigating Milat, the police discovered that in 1971 he had been charged with the abduction of two women and the rape of one of them, although the charges were later dropped due to lack of evidence. Milat also worked on the highway between Sydney and Melbourne (where several of the victims disappeared), he owned property in the vicinity of Belanglo Forest, and he had sold a Nissan Patrol four-wheel drive vehicle shortly after the discovery of the bodies of Clarke and Walters (this was the exact same type of vehicle as theirs). On May 5, 1994, Onions positively identified Milat as the man who had picked him up and tried to kill him, and Milat was arrested on May 22. The search of his home revealed a huge collection of weapons, including parts of a .22 calibre rifle that matched the type used in the murders, plus clothing, camping equipment and cameras belonging to several of his victims. In March 1996 the trial finally opened. Lasting fifteen weeks, Milat's defence argued that in spite of the amount of evidence, there was no proof Milat was guilty and attempted to shift the blame to other members of his family, particularly his brother Richard. But on July 27, a jury unanimously found Milat guilty. For the seven murders, he was given a life sentence on each count, with all sentences running consecutively and without the possibility of parole. He was also convicted of the attempted murder, false imprisonment and robbery of Paul Onions, for which he received six years' jail for each charge. In short, Milat will spend the rest of his natural life behind bars. After the trial, media tracked down Ivan's brother Richard, who was living in a secret location due to death threats. When asked about the case he said that the horrific actions carried out by Millat in New South Wales were nothing compared to what he had done in previous years. Richard also claimed that Millat had killed a total of 28 people, not 7 as he was convicted of, however, he was unable to provide any further details.
In relation to how this case manifested itself in Wolf Creek, it is worth pointing out that according to the film's official website, during the investigation, Dr. Milton, the forensic psychologist working on the case, was asked to summarize the motives of the killer. He did so with a single word - "pleasure" (in the film, Mick Taylor (John Jarratt) seems to thoroughly enjoy his 'work', taking great pleasure from torturing, first Kristy and then Liz, and then pursuing Kristy on the highway). Additionally Milat kept the possessions of his victims, having a specific predilection for video cameras (as does Mick in the film). Milat also stabbed Joanna Walters in the lower spine, probably causing immediate physical paralysis (exactly as Mick does to Liz in the film). Finally, the sign at the entrance to Mick's site reads Navithalim Mining Co. 'Navitalim' is Ivan Milat spelt backwards.
See here for a lengthy article about Milat, and here & here for an interview with Milat himself.
The other major event to influence the film was the Bradley John Murdoch case involving Joanne Lees and Peter Falconio. Lees and Falconio were British tourists backpacking in Australia. Whilst travelling along the Stuart Highway, near Barrow Creek in the Northern Territory on July 14, 2001, they were stopped by a man who was indicating that they were having trouble with their car's exhaust. Falconio got out to investigate, and Lees heard a gunshot. The man then dragged her from the car, tied her up, and blindfolded her, before forcing her into his van along with Falconio's dead body. Whilst he was driving however, Lees managed to escape into the bush. Now in the dead of night, she hid and watched as the man and his dog attempted to find her. Eventually after the man left the area, Lees hailed down a passing car, and contacted police. A massive search was initiated for Falconio's body and the murderer. But almost immediately, the world media began to point the finger at Lees herself. Expert Aboriginal trackers had been sent to the scene where Lees had hidden from the man but could find no sign of tracks other than Lees' own in the vicinity. They also failed to find any fresh blood where the car had been stopped. Two years later, with many now firmly believing that Lees herself had killed Falconio, Bradley John Murdoch was charged with rape in Barrow Creek on or around July 14, 2001. Murdoch was found not guilty of the rape, but Lees identified his photograph as being the man who abducted her, and DNA tests then confirmed that the bloodstains on Lees' clothing matched Murdoch's DNA.
Murdoch's trial began on October 18, 2005. The jury was out on December 13, and returned with a verdict of guilty on the same day after only 8 hours of deliberation. Murdoch was also convicted of other assault-related charges on Lees, and was sentenced to life imprisonment with a non-parole period of 28 years.
Falconio's body has never been found, and there is still a great deal of speculation about the truth of the case. Murdoch has always maintained his innocence, and during the trial his defence team claimed that police procedures were not followed correctly, that Lees' story was inconsistent, and that it was impossible for him to have committed the crime. The defence also discovered that Lees had been cheating on Falconio during their time in Australia, something she denied until confronted with incontrovertible evidence. It was also pointed out how much money Lees has made from the incident; $125,000 AUD for an interview with Martin Bashir and $650,000 AUD advance for a book. Lees was also forced to admit to using ecstasy and marijuana during her visit to Australia, all of which undermined her credibility as a witness. Murdoch's team argued that the whole thing was a cover up: "Peter Falconio faked his own death, and when Peter Falconio and Joanne Lees stopped by the side of the road near Barrow Creek, it was to meet with a third man, of description unknown, in order to take Peter Falconio away, alive. Police planted evidence, with the assistance of Murdoch's former drug-running partner James Hepi, who had both motive and opportunity to frame Murdoch, after Murdoch had been central to Hepi's arrest". Despite the defence's arguments however, the evidence against Murdoch, most notably the presence of his blood on Lees' clothing, was enough to convince the jury that he was the killer. However, it is worth pointing out in relation to the DNA that the technique used to collect and identify the evidence is itself not entirely without question. Low copy number DNA is a technique which can use minute amounts of DNA to identify a sample, however, not everyone agrees that it is a valid technique. At the trial of Sean Hoey in Northern Ireland in December 2007, where Hoey was charged with 29 murders related to the Omagh bombing, the primary evidence against him was based upon LCN. Hoey's defence team however had several experts testify that LCN is unreliable as an identificatory technique, and Hoey was found not guilty on all charges. The judge was highly critical of the prosecution for relying on such a technique, and subsequently, LCN was suspended by the British police (although it was reinstated, with modifications, several months). Based upon the outcome of the Hoey trial, it is believed that Murdoch is currently filing an appeal against his conviction.
As an aside, it is worth noting that Murdoch's trial was still under way at the time of the film's initial release in Australia, and for this reason the Northern Territory court placed an injunction on the film's release in that area, believing that it could influence the outcome of the trial if shown.
See here for a website dedicated to the Falconio case and here for a 2006 interview with Lees.