A native of Woodland Hills, California, and a graduate of Santa Monica High School, Skaggs was a supplemental first-round selection for the Angels in the 2009 Major League Baseball draft.

After two consecutive appearances at the All-Star Futures Game in 2011 and 2012, Skaggs made his major league debut on August 22, 2012, against the Miami Marlins.

In December 2013 the Diamondbacks traded Skaggs back to the Angels, and he served as the fifth member of the team's starting pitching rotation until an ulnar collateral ligament (UCL) injury and subsequent Tommy John surgery derailed his season on July 31, 2014.

An autopsy concluded at the end of August that Skaggs had accidentally died of asphyxia after aspirating his own vomit while under the influence of fentanyl, oxycodone, and alcohol.

[7] Santa Monica athletic director Norm Lacy once called Skaggs the school's best baseball player since Tim Leary,[9] who helped pitch the Los Angeles Dodgers to victory in the 1988 World Series.

With these five selections, they drafted two outfielders, Randal Grichuk and Mike Trout; and three pitchers: Skaggs, Garrett Richards, and Tyler Kehrer.

[12] He had committed previously to play college baseball for Cal State Fullerton, but he chose to sign with the Angels on August 7, 2009, for a $1 million bonus instead.

[17] In 2010 Skaggs and Trout lived as roommates while they played for the Cedar Rapids Kernels of the Class A Midwest League, befriending each other and the family that had rented out their basement to the players.

In exchange for Haren the Diamondbacks received pitcher Joe Saunders, prospects Patrick Corbin and Rafael Rodríguez, and a player to be named later, speculated to be Skaggs.

[22] Once Skaggs was eligible to be traded, the Diamondbacks assigned him to the Class A South Bend Silver Hawks of the Midwest League.

[30] Skaggs was one of five players to appear in both the 2011 and 2012 MLB All-Star Futures games, the others being Nolan Arenado, Manny Machado, Wil Myers, and Jurickson Profar.

[31] The Diamondbacks called Skaggs up to the major leagues on August 21, 2012, to start the first game of a same-day doubleheader against the Miami Marlins.

[41] Skaggs was named to the Angels' opening day roster that spring, joining a rotation that also featured Santiago, Jered Weaver, C. J. Wilson, and Garrett Richards.

[45] After MRI tests revealed a strain to the common flexor tendon of Skaggs's arm, the Angels placed the pitcher on the 15-day disabled list.

[46] On August 10 the team revealed he had sustained a partial tear of the ulnar collateral ligament and would need to undergo a season-ending Tommy John surgery to repair his arm.

A bout of biceps tendinitis in April set back Skaggs's recovery, but by July, he was able to begin rehab assignments with the Class-A Advanced Inland Empire 66ers and with the Bees.

[50] He made his first major league start since undergoing surgery on July 26, 2016, pitching seven scoreless innings in a 13–0 win against the Kansas City Royals.

[52] The injury kept him out of the lineup for fourteen weeks after he suffered a recurrence of oblique pain shortly before a scheduled rehab assignment in July.

[55] On April 12, 2019, Skaggs sprained his left ankle in the fourth inning of a game against the Chicago Cubs when he landed in a divot on the pitcher's mound at Wrigley Field.

In the final start of his career Skaggs threw 91 pitches in 4+1⁄3 innings against the Oakland Athletics, and sportswriter Nathan Fenno observed him to be less effective than he had been throughout the season.

[60] A 2009 MLB scouting report described Skaggs as a "young Barry Zito type", a "decent lefty" with "two above-average pitches".

[63] By 2014, his main pitches included a 94 mph (151 km/h) four-seam fastball, a curveball, and a changeup, occasionally utilizing a sinker as a self-proclaimed "secret weapon".

[66] He continued to fall back primarily on his fastball and curve after returning to the mound, but began reintegrating his changeup into his pitching rotation during the 2018 season.

[61] The Angels had been in Arlington, Texas, to play a four-game series against the Rangers, and Skaggs was scheduled to start the Fourth of July game.

[77] The Drug Enforcement Administration (DEA) later determined that fentanyl, a synthetic opioid 30 to 50 times more potent than heroin, was the primary contributor to Skaggs's death, and that he likely would have survived if not for the substance.

Corbin, Ryan Braun, Jesse Chavez, Jack Flaherty, Max Fried, Lucas Giolito, Scott Heineman, Mike Moustakas, and Christian Yelich also wore nicknames that honored Skaggs.

His first pitch against George Springer of the Houston Astros was Skaggs's signature overhand slow curveball, and it went intentionally unchallenged with no swing.

[94] During the trial, Skaggs's teammates Matt Harvey, Mike Morin, Cam Bedrosian, and C. J. Cron testified that Kay had provided them with oxycodone pills.

[101] The lawsuit accused the team of allowing Kay, who had a history of substance abuse, "unrestricted access" to members of the Angels, who were "at risk of turning to medication to assist with pain management" because of the "rigors of a 162-game schedule".

[102] The circumstances of Skaggs's death prompted MLB to consider adding random opioid screenings to the league's drug testing program.