The team plays its home games at Mustang Memorial Field, at the NCAA Division I FCS level in the Big Sky Conference.

During this time, All-American Stan Sheriff became Cal Poly's first player to join an NFL roster, beginning with the Pittsburgh Steelers in 1954.

"[4] Joining Madden and Jeter on the Mustang roster was quarterback and defensive back Bobby Beathard, who would be inducted into the Pro Football Hall of Fame in 2018 as the architect and general manager responsible for building the Washington franchise into a perennial Super Bowl-winning and contending dynasty.

[5] Tragedy struck in 1960 following a game at Bowling Green State University on Saturday, October 29, 1960, when a plane leaving Toledo Airport crashed, killing 22 people.

[7] Under Harper, Cal Poly produced an 8–0–1 regular-season record in 1972 and received a trip to the Camellia Bowl to play in the Western Regional Championship Game of the NCAA's College Division.

[10] Mustang safety Chris Jones had two interceptions in the game, while fullback Paul Dickens led the offense by rushing for 163 yards on 35 carries.

Cal Poly defeated Eastern Illinois in the championship game[12] on ABC and would finish the season with a 10–3 record that included a win over eventual-Division I-AA national champion Boise State.

[19] The defensive front was led by lineman Pat Moore, who received an invitation to the NFL Scouting Combine after compiling 67 tackles and 9.5 sacks during the 1990 season.

In 1994, Cal Poly would make the jump to Division I-AA (now Football Championship Subdivision) with head coach Andre Patterson at the helm.

[27] Rich Ellerson, credited by Sports Illustrated for his role in refining Arizona's versatile "Desert Swarm" defense[28] featuring Tedy Bruschi, was introduced as Cal Poly's new head coach on December 6, 2000.

[35] During the next two years, Cal Poly would experience continued success on the field and another NCAA first as two more players would win the Buchanan Award: Chris Gocong in 2005 and Kyle Shotwell in 2006.

[37] (Noble had arrived at Cal Poly after setting the San Bernardino County single-season rushing record, amassing 2,256 yards at Barstow High in 2003, fourth-most in the entire state.

At the conclusion of the 2008 season, with three conference titles, two postseason appearances, multiple All Americans developed and a record of 56–34, Ellerson departed California's Central Coast as he accepted an offer to become the head coach of Army.

[49] In 2009, Tim Walsh, the offensive coordinator for the Army Black Knights during the 2007 and 2008 seasons, was hired as Cal Poly's 16th head coach.

On November 12, 2011, Cal Poly set an all-time single-game FCS/I-AA record for most team rushes, running 95 times for 405 yards against Eastern Washington.

[50] The 2012 season proved to be the most successful of Walsh's coaching career, as his Mustangs finished 9–3, in a three-way tie for the Big Sky Conference football title and earned and an NCAA FCS playoff invitation.

[54] In 2014, Cal Poly quarterback Chris Brown became the first player in the school's Division I-era history[55] to throw for a touchdown and score TDs on both a run and a reception in the same game, as he achieved the rarity in a 30–24 victory at Weber State.

On October 15, 2016, Cal Poly set a Big Sky single-game record for passing accuracy, as former MaxPreps National High School Player of the Year[57] Dano Graves led a 13-of-14 day for a .929 completion percentage[58] in a 55–35 win over Portland State.

[61] Also in 2018, Mustang quarterback Khaleel Jenkins set an all-time single-season Big Sky Conference record for TD/pass attempts/INT ratio, not throwing any interceptions among his 89 passes[62] (nine of which went for touchdowns,[63] including four to J. J. Koski, who went on to play for the L.A. Rams[64]).

The program dealt with multiple starts, stoppages and restarts to practice schedules amid COVID-19,[68] going a combined 2-12 during the next 24 months overall, beginning with the lack of a traditional spring calendar in 2020.

Two Cal Poly freshmen, edge Elijah Ponder and punt returner Giancarlo Woods, were selected to the Phil Steele Magazine Freshman All-America Team in January 2022.

In June 2022, a replacement of the then-Alex G. Spanos Stadium field was completed, as Cal Poly joined the rest of its peers in the Big Sky as having a turf surface.

[74]Cal Poly started the 2022 season 1-1, with quarterback Jaden Jones winning the Big Sky Conference Offensive Player of the Week award for September 12.

[76] Midway through the year, the university announced the upcoming addition of a John Madden Football Center, a total $30-million training facility adjacent to the stadium, set to complete construction in 2024.

[78][79] Meanwhile, the Mustangs also suffered more injuries across the lineup, and started a combined seven total backup linemen the rest of the fall, ultimately finishing 2–9 in closing the year with a 49–42 victory over Portland State.

Additionally, Cal Poly renovated the lower portion of the older east-side bleachers to add handicapped seats and improve accessibility and egress.

In November 2022, the university announced the facility would be renamed Mustang Memorial Field Presented by Dignity Health French Hospital Medical Center, reflecting a new 10-year naming rights agreement between the college and the healthcare organization.

USD and Cal Poly have a regional rivalry, as both schools are in-state FCS opponents south of the Bay Area, despite residing in different conferences.

Cal Poly's band is a popular staple at home football games, performing a wide variety of halftime shows and postgame renditions, along with in-game music following first downs, touchdowns and significant defensive plays.