[6] The Los Angeles Dodgers selected Piscotty in the 45th round of the 2009 Major League Baseball draft but he opted not to sign.

[13][14] After playing in the infield for the Quad Cities River Bandits of the Single–A Midwest League in 2012, the Cardinals moved him to the outfield before the 2013 season.

[21] He made his major league debut that night as the starting left fielder against the Chicago White Sox in an 8–5 win, and singled off Carlos Rodón in his second at-bat for his first hit.

[22] His sacrifice fly scored Peter Kozma on July 25 and was the only run of the game and game-winner in a 1–0 win over the Atlanta Braves for his first RBI.

[23] His first home run came at Busch Stadium on August 16 in a 6–4 loss to the Miami Marlins,[24] and he hit his first triple the next day in a 2–1 win over the San Francisco Giants.

[25] Piscotty set a career-high five RBI on August 23 against the San Diego Padres at Petco Park, including his first career multi-home run game, while adding a triple.

[26] The first four-hit game of Piscotty's professional, and major league, career was in 6–0 win over the Giants at AT&T Park on August 29.

[27] While playing the Pittsburgh Pirates on September 28, Piscotty was injured on a fly ball into left field when he collided with Peter Bourjos' knee, which hit him in the head.

[20] He lost to the winner of the National League Rookie of the Year Award to Cubs' third baseman Kris Bryant.

[33] While facing Max Scherzer of the Washington Nationals on May 27, Piscotty hit his first career grand slam in a 6–2 win.

Five years prior, the Cardinals plucked Piscotty out of Stanford University with one of the two picks they netted as compensation for Albert Pujols' departure.

[41] Piscotty returned from the DL, and was subsequently optioned to Triple-A Memphis due to his underachieving year, with a .232 batting average.

On December 14, 2017, the Cardinals traded Piscotty to the Oakland Athletics in exchange for Yairo Muñoz and Max Schrock.

[42] The trade came at the request of Piscotty who wished to be closer to his mother, Gretchen, who was battling amyotrophic lateral sclerosis (ALS).

{https://www.baseball-almanac.com/players/player.php?p=piscost01} Piscotty hit two grand slams in 2020, the first of which gave the Athletics a 5–1 walk off win against the Texas Rangers on August 4.

The second was hit 10 days later against the San Francisco Giants to tie the game in the ninth inning, which the A's began trailing 7–2.

[53] On March 30, after not making the Opening Day roster, Piscotty requested and was granted his release by San Francisco.

[56] On February 3, 2024, Piscotty signed a minor league deal with the Oakland Athletics, which included an invitation to spring training.

As of September 2013, he is thought to have a hit tool and approach that should help him get to the Major Leagues, but scouts are unsure if he will develop the type of power that is associated with corner outfield positions.

[64] Piscotty owned a $1.4 million home in Creve Coeur, Missouri while playing for the Cardinals, but sold it after being traded.