Niekro was drafted by the Cleveland Indians in the seventh round of the 1966 amateur draft, but he did not sign with the club. On June 7, he was drafted in the third round of the draft by the Chicago Cubs. Niekro went 10–7 in 1967, throwing 169.2 innings while having a 3.34 ERA and 77 strikeouts. The season after, he went 14–10 while throwing 177.1 innings on a 4.31 ERA while having 65 strikeouts. On April 25, 1969, he was traded to the expansion San Diego Padres along with Frankie Libran and Gary Ross for Dick Selma. His combined total for the season was 8–18, throwing 62 strikeouts in 221.1 innings while having a 3.70 ERA. Along with Al Santorini, he led the Padres in wins with eight. He was traded by the Padres on December 4 to the Detroit Tigers for Dave Campbell and Pat Dobson. In three seasons with Detroit, he went 21–22, having his best season in 1970 by going 12–13, although he had a 4.06 ERA in 213 innings, with a high of 101 strikeouts. He threw 122 innings in the next season and just 47 in the following. He was selected off waivers by the Atlanta Braves on August 7, 1973. Niekro used a fastball and a slider early in his career, with mixed results. In his two seasons with the Braves, he went a combined total of 5–6 while having a 3.76 ERA and 67 innings pitched. During his tenure, he got re-acquainted with the knuckleball that their father taught them. The knuckleball became an essential part of his arsenal though never his sole pitch. Joe threw harder than Phil and could set up batters nearly as effectively with his fastball in combination with his excellent changeup.\n', '

The Houston Astros purchased Niekro\'s contract from the Braves for $35,000 in 1975. He blossomed into a dominant pitcher as he perfected his knuckleball in Houston, going 21–11 in 1979 and 20–12 in 1980, to become the first Astros pitcher to win 20 games in consecutive seasons. He also made the National League All-Star team in 1979, a season in which he led the league with his 21 wins and five shutouts, won the TSN Pitcher of the Year Award, and ended second in voting for the Cy Young Award behind Bruce Sutter. 1979 also saw the Niekro brothers tie for the wins leader in Major League Baseball, marking this the only year that two brothers shared this honor.\n', '

In 1980, Houston had a three-game lead over the Los Angeles Dodgers in the National League West, then lost their last three games of the regular season in Los Angeles, to force a one-game playoff. Niekro allowed six hits in a 7–1 Houston victory that propelled the Astros to their first postseason. He then pitched 10 shutout innings in Game 3 of the NLCS, with the Astros eventually winning 1–0 in the eleventh inning, though they lost the series in five games to the Philadelphia Phillies. He went 9–9 in 1981, throwing a 2.82 ERA in 166 innings, although he struck-out just 77 batters. He appeared in Game 2 of the 1981 National League Division Series against the Los Angeles Dodgers, pitching eight scoreless innings, although Joe Sambito ended up being the winning pitcher for the Astros as they won in the eleventh inning, though the Dodgers would win the series in five games. In his next three seasons, he won over 15 games in each, although his ERA was inconsistent, being as low as 2.47 in 1982 and as high as 3.48 in 1983. He threw a career high of 16 complete games and 130 strikeouts in 1982.\n', '

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