Born in the Chicago suburb of Waukegan in 1897, O'Farrell was a prep star of some renown. He also played in the semi-pro Lake Shore League. In 1915, Chicago Cubs owner C. Webb Murphy signed the phenom to a big league contract. "Right off the sand lots into the big leagues," noted the 1933 Who's Who in Major League Base Ball. "When I was finishing high school, I was just as rabid a White Sox fan as ever," O'Farrell recalled in The Glory of Their Times (William Morrow and Company, 1984). "I was catching for the local Waukegan semipro team then, and one day in the middle of the summer we played an exhibition game with the hated Chicago Cubs. Well, lo and behold, after the game the Cubs offered me a contract! I grabbed it up, and suddenly, after all those years of being a White Sox fan, there I was, of all things, a Cubs fan!" 

As one of four catchers on the Cubs roster (including player-manager Roger Bresnahan), O'Farrell had no chance of breaking into the everyday lineup. In 1915, he appeared in 2 games, recording his first Major League hit in three at-bats. In 1916 he appeared in 1 game before the Cubs shipped him to Peoria of the Illinois-Indiana-Iowa League. Still, the experience proved valuable. O'Farrell recalled that Bresnahan "more or less showed me the ropes and taught me how to catch." The 18-year-old backstop, though, found few friends in the Cubs clubhouse. "I didn't get in many games. I was straight out of high school, and mostly I just sat around and watched. Of course, aside from Bresnahan, nobody helped me any. They didn't want a rookie to come in and take one of their buddies' jobs. But they weren't too bad. They just more or less ignored me."

In Peoria, O'Farrell appeared in 77 games. In 223 at-bats, he finished with 29 runs, 64 hits, and a .287 average. In the 1916 season, the 84-50 Peoria Distillers (there were several large breweries in the central Illinois city) captured the pennant, comfortably ahead of the second-place Hannibal Mules (79-57). Joining O'Farrell on the Distillers roster was shortstop Charlie Hollocher. The two would room together as teammates in Chicago. Hollocher's promising career was cut short due to a nervous condition, and he committed suicide in 1940. As America's entry into World War I loomed, O'Farrell returned to Peoria for a second season in the Class B Three Eye. He showed continued sign of improvement, batting .318 with 24 runs and 57 hits in 52 games. 

On April 6, 1917, the U.S. declared war on Germany, and tens of thousands of men enlisted or found employment in wartime industries. That summer, low minor leagues throughout the nation succumbed to the manpower shortage: the Class C Virginia League disbanded on May 16; Class D Georgia-Alabama League on May 23; Class D North Carolina State League on May 30; Class D Central Texas League on June 6; Class D Northern league on July 2; Class D Dixie League July 5; Class B Northwestern League on July 17; and Class D Central Association on August 7. The Three-I League was yet another casualty of the war, and on July 8, the Class B loop suspended play. That same day, South Bend of the Central League relocated its franchise to Peoria, and O'Farrell remained in the city to play Class B baseball, albeit in another circuit. In 58 games in the Central League (affiliates included Evansville, Ft. Wayne, and Grand Rapids), he batted .283 with 22 runs and 57 hits. At the end of the season, the Cubs recalled the now 20-year-old backstop, and he appeared in 3 games, smacking 1 single and 2 doubles in 8 at-bats.

In Eugene Murdock's 1991 oral history Baseball Players and Their Times, O'Farrell recalled his playing days in the Three Eye. "Well, we didn't live very high. We traveled on those old 'rattler' trains, you know. The towns weren't too far apart so we traveled mostly in the daytime, but it was hot. Really brutal, but I didn't mind that much. We were all young and I was so glad just to be playing ball. I would have played for nothing, if it had to be that way . . . . Ball parks were not much. They were wooden and seated a couple of thousand people, maybe. But they were good enough for that level of play."

In 1918, O'Farrell was in the big leagues to stay. He appeared in 52 games (45 behind the plate), sharing catching duties with veteran Bill Killefer. O'Farrell, playing his true rookie season, finished with 115 putouts, 36 assists, 4 errors, and a .974 fielding percentage. From 1919 through 1923, he caught 463 games. "Those were the days when catching was really rough," he remembered. "There were so many off beat pitches then, you know. Like the spitball, the emory ball, the shine ball. You name it, somebody threw it." In 1924, a foul tip shattered O'Farrell's mask, knocking him unconscious and fracturing his skull. While he recuperated, 23-year-old Gabby Hartnett earned praise as the Cubs backstop of the future. 

On March 23, 1925, Chicago sent O'Farrell to the St. Louis Cardinals. In 1926, he enjoyed his finest season, appearing in a remarkable 146 games behind the plate for the World Series champion Redbirds. He batted .293 with 144 hits, 30 doubles, 7 home runs, and 68 RBI. Behind the plate, he finished with 466 putouts, 117 assists, and 10 errors (.983). For his iron man performance he received N.L. MVP honors.

In the 1926 World Series against the New York Yankees, O'Farrell recorded 7 hits, 2 runs, and 2 RBI. Grover Cleveland Alexander earned complete-game victories in the second and sixth games. In the deciding game at Yankee Stadium, New York, down 3-2, loaded the bases in the seventh inning. At the plate was Three Eye veteran and future hall of famer Tony Lazzeri. Player-manager Rogers Hornsby then signaled for Alexander to relieve the struggling Jesse Haines. The 39-year-old Alexander, who had spent the previous night on one of his famed benders, was fast asleep in the bullpen. After being roused awake, he shuffled to the mound. "Can you do it?" wondered Hornsby. "I can try," was the response. Alexander stuck out Lazzeri in three pitches. In the bottom of the ninth inning, with the Cardinals still up 3-2 and Alexander still on the mound, Babe Ruth walked with two out. With Bob Meusel at the plate, Ruth sprinted to second. O'Farrell fired the ball to Hornsby and the World Series was over.

"You know, I wondered why Ruth tried to steal second then." O'Farrell recalled long after that epic contest. "A year or two later I went on a barnstorming trip with the Babe and I asked him. Ruth said he thought Alex had forgotten he was there. Also that the way Alex was pitching they'd never get two hits in a row off him, so he better get in position to score if they got one. Well, maybe that was good thinking and maybe not. In any case, I had him out a mile at second."

After the season, Cardinals owner Sam Breadon sent player-manager Hornsby to the Giants for Frankie Frisch and Jimmy Ring. The trade was the outcome of a longstanding feud between the obstinate owner and his outspoken manager. Breadon tabbed O'Farrell to replace the popular Hornsby. In 1927, the veteran backstop caught 53 games as his Cardinals finished with 92 victories and 61 defeats, 1.5 games behind the pennant-winning Pirates. In November, the Cardinals dumped O'Farrell in favor of Bill McKechnie. And in May 1928, Breadon sent his former MVP catcher to John McGraw's Giants, where he remained though the 1932 season. On May 8, 1929, O'Farrell caught Three Eye veteran Carl Hubbell's 11-0 no-hitter against Pittsburgh. In his final three years in the big leagues, O'Farrell returned to St. Louis (twice) and Chicago. For much of the 1934 season, he acted as the Cincinnati Reds player-manager.

He finished his big league career with 517 runs, 1,129 hits, 549 RBI, and a batting average of .273. Behind the plate, he tallied 4,295 putouts, 980 assists, and a fielding percentage of .976. He never played a single game in another position. O'Farrell then extended his playing days in the International League, appearing in a combined 172 games in 1936 and 1937.

In 1938, he returned to his minor league roots and led Bloomington to a disappointing seventh-place finish in the eight-team league. The previous season, the Bloomers struggled at the gate and folded in early July. With O'Farrell at the helm and an agreement with Milwaukee of the American Association to support the struggling franchise, there were high hopes for the Bloomers. Yet by the following season, O'Farrell was gone and Bloomington, one of the league's founding members, was playing its final season in the Three Eye.

O'Farrell died on February 20, 1988 in Waukegan. He was 91. "I did get a little discouraged at times, but I guess you do in any job," reflected O'Farrell. "Of course, when you play every day it gets to be sort of like work. But, somehow, way down deep, it's still play. Just like the umpire says: 'Play Ball!' It is. It's play."