Jon Lieber's journey through Major League Baseball began when he was drafted by the Kansas City Royals in the second round of the 1992 MLB Draft. However, it was with the Pittsburgh Pirates that he made his major league debut in 1994. Lieber quickly established himself as a reliable starting pitcher, known for his control and ability to eat innings. During his time with the Pirates, he developed a reputation for being a workhorse on the mound, consistently delivering solid performances.

In 1999, Lieber was traded to the Chicago Cubs, where he would spend the next four seasons. His tenure with the Cubs was marked by his best season in 2001, when he won 20 games, becoming the first Cubs pitcher to reach that milestone since 1991. That year, he was selected to the National League All-Star team, highlighting his status as one of the league's top pitchers. Lieber's ability to pitch deep into games and maintain a low walk rate made him a valuable asset to the Cubs' rotation.

After undergoing Tommy John surgery in 2002, Lieber missed the entire 2003 season. He signed with the New York Yankees in 2004, where he made a successful comeback. Lieber played a crucial role in the Yankees' rotation, helping them reach the postseason. His performance in the American League Championship Series against the Boston Red Sox was particularly noteworthy, as he delivered strong outings in a tightly contested series.

Lieber's next move was to the Philadelphia Phillies, where he signed a three-year contract in 2005. During his time with the Phillies, he continued to be a dependable starter, although injuries began to take a toll on his performance. Despite this, he managed to contribute to the team's efforts, providing veteran leadership and experience to a young pitching staff.

In 2008, Lieber returned to the Cubs for what would be his final season in the majors. Although his role was limited, he provided depth to the pitching staff and served as a mentor to younger players. Over the course of his career, Lieber was known for his control and efficiency on the mound, finishing with a career record of 131 wins and 124 losses, along with an ERA of 4.27.