Mizell was born in Leakesville, Mississippi, but started playing baseball in Vinegar Bend, Alabama, the town from which he drew his nickname.

Signed by the Cardinals in 1949, he debuted with them in 1952, ranking among the Top 10 in the National League (NL) in strikeouts for two years before spending 1954 and 1955 in military service.

They traded him to Pittsburgh early in the 1960 season, and Mizell led the NL in winning percentage (.636) as the Pirates defeated the New York Yankees in the 1960 World Series.

Six years after he threw his last major league pitch, he was elected to the House of Representatives, serving North Carolina's newly aligned 5th district.

[1] The St. Louis Cardinals held a tryout camp in Biloxi, Mississippi, in 1948, and Mizell recorded three strikeouts before a thunderstorm ended it early.

Mizell, returning from a local swimming spot, impressed Lewis again with his fastball, and the scout promised to sign him for $500 upon his graduation from Leakeville High School, which would occur later that evening.

[1] However, he went on to post a 17–7 record, finishing tied (with Wes Livengood) for fourth in the Carolina League in wins and second (behind Woody Rich) in ERA with a 2.48 mark.

[1] One night during the season, he sang country music over the public address system at South Side Park and rode around the field on a mule.

[7] He was hailed as "the left-handed Dizzy Dean" by sportswriter Red Smith, which Mizell called "a perty heavy load for a boy to tote.

"[1][8] Added to St. Louis's starting rotation for the 1952 campaign, Mizell made his major league debut on April 22 against the Cincinnati Reds.

[10] Two starts later, on May 2, he limited the Philadelphia Phillies to four hits and two runs in a complete game, winning in the ninth when Peanuts Lowrey broke a 2–2 tie with an RBI-single.

[22] With the Korean War occurring, Mizell had been drafted to serve in the United States Army as early as 1952, but he managed to get his service deferred twice because he was the support for his mother and grandmother.

[1] Mizell, who walked with a "two-furrow" stride, had to make a special effort not to step on the heels of the soldier in front of him when he was marching in ranks.

Mizell threw four no-hitters and 16 shutouts, helping the team reach the Army baseball championship tournament at Fort Belvoir, Virginia, in 1955.

[32] Assessing the Cardinals' pennant chances during 1957 spring training, manager Fred Hutchinson said, "We've got at least three pitchers capable of winning 20-Herm Wehmeier, Sam Jones, and Vinegar Bend Mizell.

Mizell spent much of the early part of the season in the bullpen, and the Cardinals even attempted to send him to Houston, but they were unable to get him through waivers.

Though many managers would have inserted a right-hander in this situation, Hutchinson left Mizell in to face him, and Hodges hit a grand slam, tying the game, which the Cardinals eventually lost 10–9.

[41] He had a pitching duel against Joe Nuxhall of Cincinnati in the first game of a doubleheader on September 1; Mizell prevailed 1–0, setting an NL record for most walks in a shutout with nine.

[14] His 14 losses tied with Bob Friend, Roberts, and Curt Simmons for third in the league (behind Kline's 16 and Johnny Podres's 15), but his 3.42 ERA ranked eighth.

[1] On May 28, they traded him and Dick Gray to the Pirates for Ed Bauta and Julián Javier, the latter of whom would reach two All-Star Games and win two World Series with the Cardinals over the next decade.

[14] Mizell started Game 3 of the 1960 World Series against the New York Yankees but was removed in the first inning, having given up three hits and a walk while only retiring one hitter.

[65] Against the expansion Houston Colt .45's on June 14, he pitched "rather well" according to sportswriter Louis Effrat, throwing six scoreless innings after starter Jay Hook was unable to record an out in a 10–2 defeat.

This time, however, he would pitch for the Columbus Jets of the Class AAA International League, and he would have to serve as an instructor until space for him became available on the team's roster.

[1] Writing in 1971, Ray Owen, sports editor for The Southeast Missourian, called Mizell "one of the best strikeout hurlers around the National League scene for a span of ten years.

[69] His delivery made it tricky to see the ball; Ken Boyer observed, "The guy shows you his glove, his rear, and somebody tells you it’s a strike.

"[95] President Gerald R. Ford, Jr., a former House colleague, appointed Mizell as Assistant Secretary of Commerce for the Economic Development Administration, a post he held from March 1975 to May 1976.

He criticized the Democrat for not owning a home in the district, calling him a "soft on defense" liberal that changed positions regularly on economic issues.

[94] Neal, a supporter of the Democratic presidential nominee Jimmy Carter,[96] polled almost the same raw vote as Mizell had four years earlier, when he was running on the Nixon–Agnew slate.

"[2] Yet Robert Mitchell, historian who studied Stephen Neal, observed that Mizell supported legislation that curtailed tobacco exports.

[8] Writing for Sports Illustrated, Robert Creamer observed, "he has an appealing drawl, a facile tongue, a warm, memorable face and that wonderful nickname.