Altherr began 2010 back with the GCL team, where in 27 games, he hit .304 with 15 RBI and 10 SB, but he struck out 22 times to just 3 walks. He earned a promotion to Short-Season Williamsport on July 22. In 28 games with Crosscutters, he hit .287 with 10 RBI, and just 13 strikeouts to 8 walks. After the season, he was rated the Phillies 10th best prospect by Baseball America.[6] Altherr began 2011 with Single-A Lakewood, but he hit poorly, hitting just .211 with 15 RBI and 12 SB in 41 games. By the time the New York–Penn League began in 2011, he was back with Williamsport, but he understood the demotion and worked to regain his confidence.[7] He was an All-Star in 2011, and in 71 games with Williamsport, he hit .260 with 5 HR, 31 RBI, and 25 SB.
Altherr was given a second shot at Lakewood, and in 110 games, he hit .252 with 8 HR, 50 RBI, and 25 SB. He played mostly left field up to 2012, but he was used mostly at center field with Lakewood. He played 2013 with High-A Clearwater, where in 123 games, he hit .275 with 12 HR, 69 RBI and 23 SB, but he struck out 140 times.
Altherr was set to begin 2014 with Double-A Reading, but he was sent to Clearwater before playing a game with Reading on April 13. However, after 7 games, he was quickly promoted back to Reading. He was hitting .245 in 52 games with 4 HR and 23 RBI, including hitting .417 with 9 RBI in his last 12 games, before he was promoted to Philadelphia.
On June 16, 2014, Altherr was recalled to Philadelphia to replace outfielder Tony Gwynn Jr., who was placed on the bereavement list following the death of his father, Tony Gwynn.[11] He made his major league debut that night, appearing as a pinch-hitter in the 12th inning against the Atlanta Braves. He flied out to center field, and was replaced by pitcher Antonio Bastardo in the lineup.[12] He was optioned back to Reading on June 19.[13]
During spring training in 2016, Altherr tore a ligament in his left wrist, requiring surgery that caused him to miss the first half of the season.[16] He was activated from the disabled list on July 28.[17]
On September 18, 2017, in a 4–3 win over the Los Angeles Dodgers, Altherr hit a grand slam, the first one ever given up by Clayton Kershaw, who was then making his 288th regular-season start, having pitched 1,917 innings in 10 seasons.[18][19] In 2017, in 372 at bats, Altherr batted .272/.340/.516 with 19 home runs and 65 RBIs.[20]
On July 22, 2018, Altherr was sent down to the Phillies Triple A Lehigh Valley Iron Pigs, but was brought back up in September. In 2018, he batted .181/.295/.333 for the Phillies with 8 home runs, 3 stolen bases, and 37 RBIs.[21] He was tied for 4th in MLB with four extra-base-hits as a pinch-hitter.[22]
On April 10, 2019, in the ninth inning of a game where the Washington Nationals were blowing out the Phillies 14–0, Altherr was called upon to pitch. He gave up one run and notched two strikeouts, with his fastball topping out at 90.5 mph.[23] On May 4, 2019, Altherr was designated for assignment by the Phillies.[24]
On May 11, 2019, Altherr was claimed on waivers by the San Francisco Giants.[25] After a single at-bat with the Giants, he was again designated for assignment on May 19.[26]
The New York Mets claimed Altherr off of waivers on May 23, 2019.[27] He homered in his first at-bat with the team, on May 25.[28] His contract was purchased on July 27.[29] Altherr was designated for assignment on August 24.[30] In 31 at bats with the Mets he batted .129/.200/.258.[31] He elected free agency on October 1.
On November 22, 2019, Altherr signed a one-year contract with the NC Dinos of the KBO League.[32] On January 1, 2021, Altherr re-signed with the Dinos on a one-year, $1.3MM contract.[33] He slashed .272/.358/.514 with 32 home runs and 84 RBIs over 143 games. Altherr was not re-signed following the 2021 season and became a free agent.[34]
On March 29, 2023, Altherr signed with the Tri-City ValleyCats of the Frontier League.[35] In 82 games for the club, he batted .294/.385/.555 with 21 home runs, 70 RBI, and 8 stolen bases. On December 15, the ValleyCats declined their option on Altherr, making him a free agent.[36]
On March 19, 2024, Altherr signed with the Algodoneros de Unión Laguna of the Mexican League.[37] In 38 games, he batted .264/.417/.512 with seven home runs and 16 RBI. On June 10, Altherr was released by the club in order to be present for the birth of his second son.[38]