In 2005 as a senior, Mustain threw for 3,817 yards and set the state's highest classification single season record with 47 touchdowns and completed 69.3 percent of his pass attempts.

[2] Springdale went undefeated with a record of 14–0 and won the Class AAAAA state title, including three wins over nationally ranked opponents and a No.

Mustain started at quarterback for the West team in the 2006 edition of U.S. Army All-American Bowl in San Antonio, Texas, where he was awarded the Hall Trophy as National High School Player of the Year.

Mustain was the top quarterback in the nation coming out of high school in 2006,[4] and was considered a better prospect than eventual Heisman Trophy-winner Tim Tebow.

[2] In recognition of his accomplishments, Springdale Mayor Jerre Van Hoose declared December 6, 2005 "Mitch Mustain Day" in the city.

[2] Mustain enrolled at the University of Arkansas on July 10, 2006, and, in his first game on September 2, 2006, replaced starting quarterback Robert Johnson in the fourth quarter of an eventual 50–14 loss to the USC Trojans.

The following day, Arkansas head coach Houston Nutt named Mustain as the starting quarterback for the next game against Utah State, moving Johnson to wide receiver.

11 Arkansas' 26–20 win over South Carolina, when Mustain was relieved after one series by sophomore Casey Dick, who led the Razorbacks for 228 yards and a touchdown.

[11] On Dec 20, Nutt announced that Dick would start for the Razorbacks in the Jan 1 Capital One Bowl against the Wisconsin Badgers; however, he stated that Mustain would also enter the game in the third series.

[2] After the initial denial, Mustain went to two Arkansas boosters for guidance, and they and his mother, Beck Campbell, met with Nutt and Athletic Director Frank Broyles to secure the transfer.

As a result, Mustain and redshirt freshman Aaron Corp began alternating repetitions with the first team offense and competing for the possible starting spot.

[31] Mustain went undrafted in the 2011 NFL Draft, and signed a 10-day free agent contract with the Hamilton Tiger-Cats of the Canadian Football League on June 1, 2011, to see if he could win a backup job.

[2] Mustain then applied to Marine Officer Candidates School and worked at a friend's car dealership in Bentonville before signing with a new team in September.

[32] In January 2013, Mustain signed with the San Jose SaberCats to backup legendary Arena Football League quarterback, Aaron Garcia.

[33] In April 2013, the Sabercats signed Russ Michna as their new starting quarterback, while Mustain remained the backup and Garcia was traded.

Mustain, who had not pitched since high school, threw a 90 mph fastball at a tryout in front of a White Sox scout in January 2012.

[41] On June 19, Mustain made his professional debut for the rookie-level Bristol White Sox against the Bluefield Blue Jays.