Rose was born April 14, 1941, in Cincinnati, Ohio, one of four children born to Harry Francis "Pete" and LaVerne Rose. He was a member of the Order of DeMolay as a young boy and was encouraged by his parents to participate in sports. He played baseball and football at Western Hills High School. Although Rose was small for his age, he earned the starting running back position on his freshman football team.

During a spring training game against the Chicago White Sox in 1963, the Reds' regular second baseman, Don Blasingame, pulled a groin muscle; Rose got his chance and made the most of it. During another spring training game against the New York Yankees, Whitey Ford gave him the derisive nickname "Charlie Hustle" after Rose sprinted to first base after drawing a walk. Despite (or perhaps because of) the manner in which Ford intended it, Rose adopted that nickname as a badge of honor. In Ken Burns' documentary Baseball, Mickey Mantle claimed that Ford gave Rose the nickname after Rose, playing in left field, made an effort to climb the fence to try to catch a Mantle home run that everyone could see was headed over everything. Rose made his major league debut on April 8, 1963 (Opening Day) against the Pittsburgh Pirates and drew a walk in his first plate appearance. After going 0-for-11, Rose got his first Major League hit on April 13, a triple off Pittsburgh's Bob Friend. He hit .273 for the year and won the National League Rookie of the Year Award, collecting 17 of 20 votes. Rose entered the US Army Reserves after the 1963 baseball season. He was assigned to Fort Knox for six months of active duty, which was followed by six years of regular attendance with a 478th Engineering Battalion USAR at Fort Thomas, Kentucky. At Fort Knox, he was a platoon guide and graduated from United States Army Basic Training January 18, 1964, one week before his marriage to Karolyn. Rose then remained at Fort Knox to assist the sergeant in training the next platoon and to help another sergeant train the Fort's baseball team. Later in his Fort Thomas service, Rose served as company cook which entailed coming in early for the one weekend/month meeting so that he could get out early enough to participate in local Reds games. Other Reds players in the unit included Johnny Bench, Bobby Tolan and Darrel Chaney.

Where did the nickname come from
Whitey Ford gave him the derisive nickname "Charlie Hustle" after Rose sprinted to first base after drawing a walk.