Originally a pitcher, the native of Kansas City, Missouri had his breakthrough season in 1911 in which he won 23 games for the Red Sox, compiled an earned run average of 2.02, threw a no-hitter against the St. Louis Browns and struck out 15 batters in a single game. The strikeout record stood until 1961. He earned the nickname "Smokey Joe" because of his blazing fastball. Legendary fastballer Walter Johnson once said, "Can I throw harder than Joe Wood? Listen, my friend, there's no man alive can throw harder than Smokey Joe Wood!" Satchel Paige concurred, saying, "Smokey Joe could throw harder than anyone." Wood once struck out 23 batters in an exhibition game.

Wood's best season came in 1912, in which Wood won 34 games, tied Johnson's record for 16 consecutive victories (and beat Johnson 1-0 in a highly publicized game that September) and went 3-1 in the World Series, including Boston's deciding Game 8 in which he beat Hall of Famer Christy Mathewson. Wood was named World Series MVP.

The following year, Wood slipped on wet grass while fielding a bunt in a game against the Detroit Tigers. He fell and broke his thumb, and pitched in pain for the following three seasons. Although he maintained a winning record and a low ERA, his appearances were limited as he could no longer recover quickly from pitching a game. He sat out the 1916 season and most of the 1917 season, and for all intents and purposes ended his pitching career.

Late in the 1917 season, Wood was sold to the Cleveland Indians, where he rejoined former teammate Tris Speaker. Always proficient with the bat, Wood embarked on a second career and, like his former teammate Babe Ruth, ended his career as an outfielder. His hitting statistics, however, were far more pedestrian than those of Ruth. Wood pitched seven more times, all but one game in relief, winning none and losing one. He also appeared in four games in the 1920 World Series.

He left the majors after the 1922 season with a career pitching record of 116-57 and an ERA of 2.03. His lifetime batting average was .283. In his final with the Indians, Smokey had his highest hit total for a season with 150 hits and also drove in his highest rbi total with 92.

Wood went on to become head baseball coach at Yale University, where he compiled a career managing record of 283-228-1 over 20 seasons.

Years later, in 1981, Wood was present at an historic pitcher's duel between Yale and Saint John's University, featuring future major leaguers Ron Darling and Frank Viola. Darling threw 11 no-hit innings for Yale, matched by Viola's 11 shutout innings for St. John's. Wood, sitting in the stands, recalled Ty Cobb and said, "A lot of fellows in my time shortened up on the bat when they had to--that's what the St. John's boys should try against this good pitcher." Darling lost the no-hitter and the game in the 12th, and Wood called it the best baseball game he had ever seen. The account was recorded in Roger Angell's 1982 book The Web of the Game, and, later, in the anthology Game Time: A Baseball Companion.

In 1984, Wood received a standing ovation on Old Timers Day at Fenway Park in Boston, some 72 years after his memorable season. Aged 94, he said he was happy that Boston remembered him as "Smokey."

Wood died in West Haven, Connecticut on July 27, 1985. He was buried in Shohola Township, Pennsylvania. In 1995, he was selected to the Boston Red Sox Hall of Fame.