Neale was born in Parkersburg, West Virginia. Although writers eventually assumed that Neale got his nickname, "Greasy", from his elusiveness on the football field, it actually arose during his youth, from a name-calling joust with a friend.
Neale spent all but 22 games of his baseball career with the Cincinnati Reds. He had a career batting average of .259 and finished in the top ten in stolen bases in the National League four times. When football season came around, often he would leave baseball and fulfill his football duties (albeit playing about 90% of a baseball season most years, with the exception of 1919 when he played the entire season, including the 1919 World Series).
At Washington & Jefferson, he led his 1921 squad to the Rose Bowl, where the Presidents played the California Golden Bears to a scoreless tie. At Virginia, Neale was also the head baseball coach from 1923 to 1929, tallying a mark of 80–73–2.
Neale later coached the independent professional Ironton Tanks with his legendary style, flair and winning ways. He and Tanks quarterback Glenn Presnell claimed victories against the NFL's second place New York Giants and third place Chicago Bears in 1930. The team folded in 1931.
Neale moved to the National Football League (NFL), serving as head coach of the Philadelphia Eagles from 1941 to 1950. Although it took Neale a while to pull together the needed talent to build a winning team, once he had the right ingredients, they stayed among the league's best for nearly a decade. From 1944 through 1949, Neale's Eagles finished second three times and in first place three times. The Eagles won the NFL Championship in 1948 and again in 1949, and were the only team to win back-to-back titles by shutting out their opponents, beating the Chicago Cardinals 7–0 in the snow ridden 1948 NFL Championship Game and the Los Angeles Rams 14–0 in the 1949 NFL Championship Game in a driving rain storm. It was the last championship for the Eagles until 1960. His offense was led by the passing of quarterback Tommy Thompson, the pass catching of future Hall of Fame end Pete Pihos, and the running of another Hall of Famer, Steve Van Buren. He tallied a mark of 66–44–5 including playoff games in his ten seasons with the club. Neale was inducted into the College Football Hall of Fame in 1967 and the Pro Football Hall of Fame in 1969. Both inductions recognized his coaching career.
Neale died in Florida at the age of 81 and is buried at Parkersburg Memorial Gardens in West Virginia.