Hensleigh graduated from the University of Massachusetts Amherst in 1981 with a degree in history. He attended the University of Virginia School of Law, received his J.D. from Tulane University Law School, and was admitted to the Massachusetts Bar in 1985. Before moving into writing, he worked as an attorney for several years. At the age of 31 Hensleigh began writing scripts and screen plays. He had previously written a novel and a three-act stage play but did not go to film school.

Hensleigh's start in the entertainment industry came writing episodes of the television series The Young Indiana Jones Chronicles. He received his first film credit in 1993's A Far Off Place, for which he wrote an early version of the script. His next two projects were Die Hard with a Vengeance and Jumanji, both of which were released in 1995. The Die Hard sequel was based on a spec script Hensleigh had originally conceived as a Brandon Lee action film before the actor's death, with the working title Simon Says. The script was considered for the fourth installment of the Lethal Weapon series before being picked up for Die Hard.

Hensleigh worked with Bay again on the 1998 disaster film Armageddon, and officially received credit for the screenplay. He helped rewrite scripts for the Jerry Bruckheimer projects, Con Air (1997) and Gone in 60 Seconds (2000), receiving executive Producer credit for those. (This credits someone whose work on the film would otherwise go unacknowledged).

Hensleigh made his debut as a Director with The Punisher in 2004, with the assistance of his wife, veteran Hollywood Producer Gale Anne Hurd. He co-wrote the script with Michael France, based on the Marvel Comics character The Punisher. Working on a tight schedule and with a relatively small budget, Hensleigh made a violent but restrained action movie that would be questionable to the spirit of the character.

At one point, he was set to write and direct Hulk, working on pre-production of that film for a year before pulling out. Some unrealized projects Hensleigh has worked on include a Gemini Man film and sequels to Jumanji and The Punisher. As of October 3, 2008, Hensleigh is developing the series Red Mars, which is based on the novel of the same name for AMC.

In 2011, Hensleigh wrote and directed Kill the Irishman, based on the book To Kill the Irishman: The War That Crippled the Mafia, about the Cleveland mobster Danny Greene who was active in the 1960 and 1970s.