Irina Mikitenko was born on 23 August 1972 in Bakanas, in what was then the Kazakh Soviet Socialist Republic. Of German heritage, she emigrated to Germany in 1996 after competing for Kazakhstan at the Atlanta Olympic Games, where she ran the 5,000 meters. She took German citizenship and represented Germany for the rest of her career.
She established herself on the track through the late 1990s and early 2000s, winning multiple German national titles in the 5,000 meters and 10,000 meters and reaching the final of both the 1999 World Championships and the 2000 Sydney Olympics. Her marathon debut came in 2005, and by 2007 she had shifted her focus entirely to the road.
Mikitenko won the London Marathon in 2008 and 2009. In September 2008, she won the Berlin Marathon in 2:19:19, setting the German national record and becoming the fourth-fastest women's marathoner in history at the time. That autumn she won the World Marathon Majors series title, worth $500,000, on tiebreaker over Gete Wami of Ethiopia. She won the WMM series three times in total.
She retired at the 2014 Berlin Marathon at age 42. Her marathon personal best of 2:19:19 remains the German national record and the World Masters record for the W35-39 age group. She was coached throughout her international career by her husband, Alexander Mikitenko.