He played in Major League Baseball (MLB) as a first baseman and designated hitter from 1965 to 1982 for the Cincinnati Reds, Houston Astros, Baltimore Orioles, and Kansas City Royals.

After his playing career, May spent several years as a hitting coach at the major league level for the Royals, Reds, Orioles and Tampa Bay Rays organizations.

However, the Cincinnati Reds organization was also interested in him, and the team signed May to an amateur free agent contract with a $12,000 bonus on June 1, 1961.

[1][5] May began his professional career in 1961 with the Tampa Tarpons in the Florida State League, a D-league affiliate of the Reds.

May's emergence in 1964 allowed him to be promoted the following year to the San Diego Padres of the Class AAA Pacific Coast League.

[7] On September 24, 1966 at Crosley Field in Cincinnati, he hit his first major league home run against Bob Shaw of the New York Mets.

Along with Johnny Bench, Tony Pérez, and Pete Rose, May helped power arguably one of baseball's great offenses.

With his pragmatic personality and comic sense of timing, manager Sparky Anderson often called on May to put out clubhouse fires.

[15] His three-run homer to left field off Eddie Watt's first pitch in the eighth inning of Game 4 led to the only Series victory for the Reds who avoided an Orioles' four-match sweep.

The Astros, badly in need of power after finishing last in the NL in home runs in 1971, completed a trade with the Reds on November 29, 1971 that sent second baseman Morgan, pitcher Jack Billingham, infielder Denis Menke, outfielder César Gerónimo and minor leaguer Ed Armbrister for May, second baseman Tommy Helms and utility man Jimmy Stewart.

[20] May was acquired along with Jay Schlueter by the Baltimore Orioles from the Astros for Enos Cabell and Rob Andrews at the Winter Meetings on December 3, 1974.

Averaging 32 homers and 98 RBI as one of MLB's top five power hitters over the previous five seasons, May was expected to improve the Orioles' offensive production at first base.

However, he is one of 11 major leaguers to reach the 100-RBI plateau playing for three teams, the others being Dick Allen, Joe Carter, Orlando Cepeda, Rocky Colavito, Goose Goslin, Rogers Hornsby, Reggie Jackson, Al Simmons, Vic Wertz, and Alex Rodriguez.

[26] The Big Bopper of Birmingham and Frank Robinson are the only players to be elected to both the Orioles and Reds Halls of Fame.

[29] After that, he began his coaching career in the Mets organization in 1999 and later worked as the minor league hitting coordinator for the Seattle Mariners from 2012–2015.

May Jr.'s son, Jacob May, played baseball at Coastal Carolina University, and was selected by the Chicago White Sox in the third round (91st overall) of the 2013 MLB Draft.

May was featured in a Sports Illustrated story written by Steve Rushin about TV character Sam Malone from the show Cheers.