He played in Major League Baseball as a catcher from 1950 through 1963 for the Cincinnati Reds/Redlegs, Chicago Cubs, St. Louis Cardinals, San Francisco Giants, New York Mets, Baltimore Orioles, and Washington Senators.

At 15, he went to Briggs Stadium and helped warmup starting pitchers for the Detroit Tigers and get Hank Greenberg into shape after he returned from military service.

[1][3] Landrith was discovered by the Cincinnati Reds after leading his Detroit team to a second-place finish in the 1948 National Junior Amateur Federation Tournament.

[12] In the opening game for Tulsa against the Dallas Eagles on April 11 at the Cotton Bowl, Landrith went 1-for-2 with a double before breaking his left ankle as he slid into home plate.

Johnny Pramesa had a sprained ankle sustained the day before on July 29, Bob Scheffing was having problems with his left elbow, and Dixie Howell's throwing hand had been sore.

[16] He attended spring training with the Reds, but at the end of March became the first player cut from the roster, being optioned to the Buffalo Bisons of the Class AAA International League.

[24] Going into the season, manager Rogers Hornsby was optimistic that they would have a better club with more power overall, citing Landrith as one of the new players that could help the 1953 Reds be a success.

[26] Landrith impressed during spring training, capping off the exhibition season with five RBIs against the Detroit Tigers with a three-run home run in a 10–9 winning effort on April 12.

[29] At the height of anti-Communism sentiment in the United States, the Reds officially changed their name to the Cincinnati Redlegs to remove any potential "confusion" between the baseball team and Communists.

[4] He did, however, have one dramatic game-winning walk-off home run against the New York Giants' reliever Al Corwin in the bottom of the 12th inning on July 19 to give the Reds a 1–0 victory.

[42] Originally, the move sparked eight-year Cub veteran Jeffcoat to announce his retirement from baseball on November 29 and go into the insurance business.

[47] Bob Scheffing was hired as new GM on October 12,[48] and the new Cubs regime made it clear that they were not satisfied with the current platoon of Landrith and Chiti working behind the plate with a combined 50 RBI, also implying that defensively the teams catching "left something to be desired.

[50] On December 11, 1956, Landrith, along with Jim Davis, Sam Jones, and Eddie Miksis was traded to the St. Louis Cardinals for Wally Lamers, Jackie Collum, Ray Katt, and Tom Poholsky.

Hal Smith was in an extended slump during the Cardinals spring training,[59] so Landrith was the opening day starting catcher on April 15 against the Chicago Cubs in a 4–0 defeat.

[4] Landrith was traded to the San Francisco Giants along with teammates Billy Muffett and Benny Valenzuela for Ernie Broglio and Marv Grissom on October 8, 1958.

What was once considered a throw-in player in a trade that was centered on reliever Billy Muffett for the Giants, club President Horace Stoneham said it was a very lucky deal for them, referring to Landrith.

[68] Landrith responded the next day by hitting a game-winning home run in the 11th inning of a spring training game off rookie Jim Brewer to help the Giants beat the Chicago Cubs 7–6.

[4] On July 19, Landrith caught for the historical debut game of legendary Dominican Hall of Fame pitcher Juan Marichal.

The Pirates were up 1–0 with 1 out in the bottom of the 11th when Landrith hit a game tying home run to deep right field off reliever Roy Face.

[86] New York manager Casey Stengel justified the choice by explaining that, "You gotta have a catcher or you're gonna have a lot of passed balls.

Landrith played at catcher in the New York Mets very first regular season game on April 11, 1962, against the St. Louis Cardinals, batting eighth in the order and going 0-for-4 in an 11–4 loss.

"[93] In typical Mets form for the inaugural season, the win was almost voided when Rod Kanehl, pinch runner for Gil Hodges, failed to touch third base after the home run.

If Landrith touched third base before Kanehl, Rod would have been called out and the Braves would have gained a win on a walk-off home run by the opposing team.

[104] He struggled with the Senators, hitting .173 with one home run and seven RBIs in 42 games before breaking his hand on a foul tip off a pitch from Steve Ridzik of the New York Yankees on August 7.

Landrith brought his playing career to a close in an AL-NL benefit game on February 14, 1965, for the widow of Red Adams, a deceased custodian at Candlestick Park, helping to raise over $8,000.

[108] Although Landrith was small for his position, standing at 5 feet 10 inches (1.78 m) and weighing 170 pounds (77 kg), he made his presence known on the field with his loud voice.

Barely a month after his first call-up to the majors with the Cincinnati Reds, he made national news for being a "Holler Guy", bringing to the league what was referred to as "a brand of on-the-field chatter which hasn't been heard since the days of Leo (Gabby) Hartnett."

It is normal for catchers to occasionally call a timeout and go the mound to talk with his pitcher, especially in crucial situations, but Hobie took this facet of the game to new extremes.

[5] Landrith was in line to become the manager of Leones de Ponce of the Puerto Rico Baseball League in the winter of 1955, but a newer regulation prevented him from being allowed to take the position.

[112] In 1998, Landrith, along with Willie Mays, Mike McCormick, Orlando Cepeda, and Dave Righetti were invited to the San Francisco Giants spring training camp as guest instructors.