Iris Kyle was born in 1974 in Benton Harbor, Michigan, the fifth of six children. Her early athletic endeavors included running cross country, basketball (point guard), and softball (shortstop). She was an All-American in basketball, and received a number of athletic scholarship offers. Iris attended Benton Harbor High School continued her education at Alcorn State University in Lorman, Mississippi, on a basketball scholarship, majoring in business administration and minoring in accounting.

Iris Kyle claims the reason she got into bodybuilding was when she moved to Orange County, California, and being surrounded by fit, healthy-looking people, she thought she could obtain a similar highly trained, sculpted physique. Iris recalls, she walked into a gym and took out a membership. "I distinctly remember being a bit overwhelmed with the facilities and the seemingly endless variety of training equipment, but I knew at that exact moment … without feeling even the slightest doubt … that I could develop the kind of physique I wanted." says Iris. She was later hired by the same gym and, as an employee, got more opportunities for training and growth. She became a voracious reader of the magazines FLEX, Muscle and Fitness, and Iron Man.

Iris recalls, "I remember the first time I saw a photograph of Lenda Murray in a magazine. I was in complete awe," Iris also recalls "I cut out that picture and placed it on my refrigerator and, from that point on, my goal was to develop a physique like hers." One day, a local promoter named Butch Dennis was in her gym and, after sizing Iris up, suggested she enter a competition he was doing in 10 weeks, the Long Beach Muscle Classic. Kyle won her first contest, the 1994 Long Beach Muscle Classic. Since 1994, Iris was advised and coached by professional bodybuilder Patrick Lynn. She earned her IFBB pro card at the age of 23 by winning the heavyweight class and overall title at the 1998 NPC USA Championship in Las Vegas.

Kyle has had a series of high placings as a professional. With the exception of the 1999 and 2008 Ms. Internationals, Iris has always placed in the top six in every IFBB pro bodybuilding competition in which she competed. At the 2000 Ms International, Tazzie Colomb and Kyle were both disqualified for diuretic use. Kyle won her first professional contest at the 2001 Ms. Olympia, winning the heavyweight title, but losing the overall Olympia title to Juliette Bergmann. Looking back, Iris maintains, "I sincerely believe that I was the rightful 2001 Overall Ms. Olympia. I’m not saying Juliette didn’t display a nice overall package; I’m just saying I believe my physique was better."

In 2002, Lenda Murray returned from retirement to reclaim her Ms. Olympia title in 2002 and 2003, with Iris coming in second both times behind her idol. In 2004, Iris won both the overall and heavyweight titles of Ms. International and went on to beat Murray and win the overall and heavyweight title of the 2004 Ms. Olympia. In 2005, Iris skipped the Ms. International, and focused defending her Olympia title. However, in 2005, the IFBB changed the rules and abolished the weight class system for Ms. Olympia, along with the new '20 percent rule' requesting "that female athletes in Bodybuilding, Fitness and Figure decrease the amount of muscularity by a factor of 20%". This allowed Yaxeni Oriquen-Garcia to win both the 2005 Ms. International and dethrone Iris at the 2005 Ms. Olympia.

In 2006, Iris rebounded by regaining both her Ms. International and Ms. Olympia titles. In 2007, she again won both Ms. International and Ms. Olympia. There was a bit of a controversy at the 2008 Ms. International. Iris was placed seventh due to "bumps" on her glutes which according to head IFBB judge, Sandy Ranalli, caused “distortions in her physique”, but rebounded at the 2008 Ms. Olympia by winning the show. Kyle went on to win both 2009 Ms. International and 2009 Ms. Olympia titles in the same year. At the 2010 Ms. International, Iris won her fifth Ms. International, surpassing Yaxeni Oriquen-Garcia's four Ms. International wins, becoming the most successful Ms. International champion ever. She has gone on to win the 2010 Ms. Olympia and 2011 Ms. International and 2011 Ms. Olympia. In 2012, she could not attend the 2012 Ms. International due to a leg injury. Iris went on to win the 2012 Ms. Olympia and regained her Ms. Intentional title in 2013. In 2013, she won her ninth overall Ms. Olympia, making her the most successful female professional bodybuilder of all time. In 2014, she won her tenth overall Ms. Olympia title, breaking her own previous record of nine overall Ms. Olympia titles.

After winning her tenth overall Ms. Olympia title, Iris stated that she was retiring from bodybuilding.

On September 25, 2015, in an interview with Dave Palumbo, Kyle announced she will be coming out of retirement to compete at the 2016 Wings of Strength Rising Phoenix World Championships.

In the Winter 2016 edition of Muscle Sport Magazine, Iris Kyle, in an interview with Joe Pietaro, criticized the IFBB for its treatment of female bodybuilders and called for the reaction of a union and ambassador for female bodybuilders.

Currently, Kyle is the most successful, male or female professional bodybuilder ever. She ranks as the best female bodybuilder in the IFBB Pro Women's Bodybuilding Ranking List.

Kyle has won seventeen overall IFBB professional titles and three IFBB professional heavyweight titles, which is more IFBB professional overall wins than any female bodybuilder. Of those wins she has ten overall Ms. Olympia titles, and has two professional heavyweight wins in her weight class. Between 2000 and 2004, there were two weight classes, and from 2001–04, there was an overall winner between the two class winners. In 2001, she won the heavyweight class, but lost the overall Ms. Olympia title to the lightweight winner Juliette Bergmann. This discrepancy has led to confusion in various sport publications as to the number of Ms. Olympia titles Kyle has won. She also has the most consecutive Olympia wins, with nine, dating 2006 to 2014. She also has seven Ms. International overall wins with one heavyweight win, more than any female bodybuilder.