Lisenbee joined the
Tupelo Wolves,
Tupelo, Mississippi, minor league team of the
Tri-State League in 1925, and was traded to the Memphis Chicks, minor league team of the Southern Association in 1926. At the age of twenty-eight, he was acquired by the Washington, D. C. Senators for $44,000, and got his first pitching start on April 23, . He led the
Washington Senators to a 6–0 victory over the
Boston Red Sox. One of Lisenbee's notable accomplishments as a rookie was his consistency against the team dubbed "
Murderers' Row". He faced the
New York Yankees six times that year and won the first five outings against this storied team. The 1927 Yankees were the object of much praise, as they established a record setting 110–44 season. The Yankee hitting was vicious and frequently devoured pitchers in one inning, but Lisenbee appeared unflappable. Lisenbee was 5–1 versus New York that season. In his first meeting with the Yankees, Lisenbee was called to the pitcher's mound to face
Babe Ruth. The Senators' starting pitcher had fallen behind 3–0 in the count and the manager told Lisenbee to walk Ruth. Lisenbee disagreed and threw three strikes in a row to retire Ruth. Hod pitched the remaining seven and two-thirds innings for the win over the Yankees and he struck Ruth out three times in a row. According to Hod's recollection, Ruth later quipped that it looked as though he was throwing balls at the plate from out of a hole. This was an apparent response to Lisenbee's scrawny appearance, or possibly his underhand or sidearm pitching delivery. Babe Ruth set the major league home run record with 60 home runs in 1927. During their sixth meeting, Lisenbee tried to sail his side-arm curveball past Ruth to no avail. For Ruth, this was a golden opportunity to connect with the ball, and the result was his 58th home run of the year. Lisenbee's first year record was 18–9 for the third place Senators, and he led the
American League with four shutouts. The following season went less favorably for Lisenbee, and in December , he was traded to the Boston Red Sox. From this point in his career, Lisenbee became a journeyman pitcher in both the majors and minors. One game in particular stands out as a low-point in his career. On September 11, , the
Philadelphia Athletics manager,
Connie Mack, tried to minimize the number of pitchers to take on a road trip, in order to save money. Lisenbee, who was 37 at the time, was forced to pitch the full nine innings. He ran into trouble and allowed a record-tying 26 hits as the Athletics lost to the
Chicago White Sox 17–2. Following his release from the Reds, he returned to his hometown of Clarksville and continued to pitch for the Clarksville Colts of the
Kitty Hawk League until he was fifty-one-years-old. He then sold the Clarksville Colts and retired from baseball. ==Later years==