[2] He also played for the Baltimore Orioles, Philadelphia Phillies, Washington Senators / Texas Rangers, Chicago Cubs, Montreal Expos, and St. Louis Cardinals.

[10][8] Knowles spent five seasons in the Orioles farm system (1961, Aberdeen; 1962–63, Elmira; 1962, Stockton; 1964–65, Rochester), with a short six game stint in 1962 on the Minnesota Twins affiliate Charlotte Hornets of the South Atlantic League.

In his five year minor league career, Knowles had a 56–33 record, with a 2.77 earned run averaged (ERA), striking out 799 batters in 852 innings pitched.

[16] Knowles made his debut with the Orioles on April 18, 1965,[1] pitching 1.2 innings out of the bullpen, and giving up five earned runs[17] before returning to the Triple-A Rochester Red Wings.

Upon completion of the International League (IL) season, Knowles received a September call back up to Baltimore.

[19] He won the season opener against the St. Louis Cardinals, pitching six innings of one-run ball as a relief pitcher to earn his first career win.

[1][9] Knowles began earning a reputation as a work-horse relief pitcher, as he was used 61 times by manager Gil Hodges in 1967.

[24] He was used 32 times in 1968, with a 2.18 ERA and four saves,[1] when his season was cut short by President Lyndon B. Johnson's reserve call-up of the USAF's 113th Tactical Fighter Wing in which he was an airman first class.

[16] On May 8, 1971, the American League West first-place Oakland Athletics acquired Knowles and Mike Epstein for Frank Fernandez, Paul Lindblad, and Don Mincher.

[9][28] Knowles only allowed four of 35 inherited runners to score,[citation needed] and earned seven saves and five wins out of a bullpen that already included Rollie Fingers and Bob Locker.

[33] Knowles made five starts for the world champion A's in 1973, pitching his only complete game shutout against the Boston Red Sox on August 14.

[36][37] With two outs in the ninth inning of Game 7, manager Dick Williams brought Knowles in to replace future hall of fame relief pitcher Rollie Fingers.

Shortly after the World Series, he, Bob Locker and Manny Trillo were dealt to the Chicago Cubs for Billy Williams.

[47] Knowles did not enjoy playing in Canada, citing taxes, language problems and political unrest in Quebec[48] as the reasons for his displeasure.

After just one season in Montreal, the Expos granted him free agency in late 1978, and Knowles signed a two-year deal with his home team Cardinals.

[16] In between, Knowles played winter ball with the Tiburones de La Guaira club of the Venezuelan League in the 1964–1965 season, where he posted a 13-9 record with a 2.37 ERA and 155 strikeouts to earn Triple Crown honors.

[51] In 1989, Knowles was hired as the Philadelphia Phillies pitching coach by the team's new general manager Lee Thomas, who had been director of the Cardinals' minor league system.

[67] Knowles was named to the Florida State League Baseball Hall of Fame in 2012 for his coaching at Clearwater and Dunedin.