Kirkpatrick played his high school career at Gadsden City High School in Gadsden, Alabama, where he was a teammate of fellow Crimson Tide players Jerrell Harris and Kendall Kelly. He completed his senior football season in the fall of 2008. Kirkpatrick participated in the 2009 U.S. Army All-American Bowl & the 2008 Alabama Mississippi All-Star Football Classic, where he was recorded at 6 ft 2 in and 180 lbs.
Kirkpatrick played his final three high school seasons at Gadsden City (35 games) and finished his career with 193 tackles, 17 interceptions, three returned for a touchdown, 36 pass breakups, two sacks, one punt return touchdown, one kick return touchdown and one receiving touchdown. After completion of his senior season he was awarded as the ASWA 6A back of the year as well as a first team all-state defensive back for the second consecutive year.
Entering February 2009, Dre Kirkpatrick was one of the most highly rated and sought after high school football recruits in the country, having been awarded a 5 star rating (the maximum) by national recruiting outlets Rivals.com and Scout.com.
Kirkpatrick was selected 17th overall in the first round of the 2012 NFL draft by the Cincinnati Bengals. On May 18, 2012 he signed a 4 year $8,600,000 contract with the Bengals which includes a $4.7 million signing bonus.