Prior to his college career, McGloin was a Pennsylvania all-state quarterback while attending West Scranton High School.

He was a three-sport (football, basketball, and baseball) stand-out at West Scranton High School from 2004 to 2008, earning ten varsity letters.

After playing behind Daryll Clark and Kevin Newsome in 2009, McGloin ended up third on the depth chart in early 2010 behind Rob Bolden, a true freshman from Detroit.

On October 23, 2010, McGloin played against Minnesota when Kevin Newsome was sidelined with stomach flu and Bolden left the game with a concussion.

Bolden started the next week against Northwestern, but was pulled from the game by coach Joe Paterno after he was sacked twice and lost a fumble.

McGloin rallied the Nittany Lions from a 21-point deficit to a 35–21 victory with four touchdown passes, a mark he matched twice his senior year but never surpassed.

[3] On November 13, McGloin scored the first passing touchdowns in Ohio Stadium by a Penn State quarterback since 1963 and put them up 14–3 over the Buckeyes at halftime.

Despite playing in only 7 of the team's 12 games, he ranked tenth in the conference in completions, attempts, yards, touchdowns, and rating, but tied for 4th in interceptions.

He went 14–29 in the blue and white game and led Penn State to a game-winning drive over in-state rival Temple in week 3.

In Week 4 against Eastern Michigan, McGloin went 14-of-17 for 220 yards, 3 touchdowns, and no interceptions, for the highest completion percentage (82.4%) and passer efficiency (249.3) by a Penn State quarterback since 2000.

[12] McGloin ended his career at Penn State with a school-record 46 touchdowns, and ranked second in school history to Zack Mills with 513-of-894 for 6,390 yards.

[18] McGloin made the team and began the season as the third-string quarterback on the depth chart, behind starter Terrelle Pryor and backup Matt Flynn.

The next week, McGloin threw a go-ahead touchdown to Marcel Reece late in the fourth quarter of a 23-19 loss to the Tennessee Titans.

In a Thanksgiving contest against the Dallas Cowboys, McGloin earned praise for his play in the loss and an honorable mention for Phil Simms's "All-Iron Award" for the most valuable player.

He played just over two quarters for an injured Carr on opening day, throwing two fourth-quarter touchdowns to Reece in the 33-13 loss to the Cincinnati Bengals, and appeared in just one other game that season.

[24] On January 1, 2017, McGloin made his first start since 2013, completing six of 11 passes for 21 yards before suffering a shoulder injury late in the second quarter and being replaced by rookie Connor Cook in a 24-6 road loss to the Denver Broncos, which cost the Raiders the AFC West championship and a first-round bye.

[33] On November 3, 2017, McGloin and T. J. Yates were both signed by the Houston Texans after a season-ending knee injury to starter Deshaun Watson.

Head coach Bill O'Brien said that Yates would be the backup to Tom Savage for the November 5 game against the Indianapolis Colts, making McGloin the third-string quarterback.

[38] McGloin declined to sign with the Alliance of American Football, which began play in February 2019 before it ceased operations in April 2019.

[52] Starting from November 2019, McGloin works alongside Shaun Gayle and Dallas Clark as in-studio analysts for Sky Sports’ NFL broadcasts.