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Fusco attended Seneca Valley Senior High School in Harmony, Pennsylvania, where he played offensive tackle. He did not play football until his junior year at Seneca Valley, stating "Sophomore year, didn’t really do nothing and football just kind of came to my attention. I always watched it on TV and I sometimes got into a ticked off mood so I wanted to get out on the field and take my frustrations out on people." Despite performing for a team that won just one of eighteen contests during his two varsity seasons, Fusco earned All-WPIAL Class AAA-1 and honorable mention Quad North All-Star honors. Fusco was also an honor roll student.

Fusco received All-American, All-Region and All-PSAC first-team accolades as a junior. Named the team captain, he also received squad MVP honors. He led the PSAC Western Division with 98 knockdowns and eleven touchdown-resulting blocks, despite the team’s lack of a strong aerial game that ranked 59th in the nation. It was his drive blocking skills that helped the team finish fifth nationally in rushing (239.54 ypg) and seventh in total offense (456.69 ypg).

On April 29, 2019, Fusco was released by the Falcons with a failed physical designation after one season while only playing and starting in seven games.

On March 14, 2018, Fusco signed a three-year contract with the Atlanta Falcons. He was named the Falcons' starting right guard to start the 2018 season, beating out incumbent starter Wes Schweitzer. He started the first seven games before suffering a season-ending ankle injury in Week 7.

On February 10, 2017, Fusco was released by the Vikings.

On May 2, 2017, Fusco was signed by the San Francisco 49ers. Fusco started all 16 games for the 49ers in 2017 at right guard, and the team averaged 3.9 yards per carry on runs behind him.

On September 6, 2014, the Vikings signed Fusco to a five-year, $25 million contract extension.

Along with Will Rackley, Ben Ijalana, and David Arkin, Fusco was considered one of the best small-school offensive line prospects. After a strong performance at the Senior Bowl and the NFL Combine, Fusco was drafted by the Minnesota Vikings in the sixth round, 172nd overall, in the 2011 NFL Draft.

He became the 19th player in school history to garner All-American first-team honors more than once in a career, as the 2010 Gene Upshaw Award winner and team captain captured All-PSAC honors for the third consecutive year. With a limited passing game, The Rock again relied on his drive blocking skills to place tenth in the Division II ranks with an average of 247.38 yards per game rushing. He capped off an excellent career by becoming the first player in school history to compete in the Senior Bowl.

After enrolling at Slippery Rock in 2006, Fusco spent his freshman season as a red shirt on the scout team, where he played offensive tackle. In 2007 spring drills, Fusco shifted to center. As a sophomore, Fusco received All-American honorable mention, All Super Region I and All Pennsylvania State Athletic Conference first-team honors. He started all eleven games at center, delivering ten touchdown-resulting blocks for a unit that rushed for 29 scores. His efforts help Slippery Rock rank second in the conference with an average of 484.14 yards per game.

Brandon Fusco (born July 26, 1988) is a former American football guard. He was drafted by the Minnesota Vikings with the 172nd overall pick in the sixth round of the 2011 NFL Draft. He played college football at Slippery Rock University of Pennsylvania.