During his senior year in 2008, Gano finished first in the FBS for field goals made, percentage of field goals converted and 50-yard field goals made, and was the Lou Groza Award winner as the nation’s top kicker. He was one of only two kickers in college to make over 90% of his field goal attempts in the 2008 season. He was the highest scoring kicker in America and fourth overall in the FBS in scoring. He was a Rivals.com, Scout.com, and CBS Sports first team All-American. Gano was listed as Walter Camp, Associated Press, Sporting News, SI.com, and Phil Steele second team All-American. He earned All-ACC First Team honors as well.

Gano was four-time ACC Specialist of the Week for his kicking performances against NC State, Virginia Tech, Clemson, and Maryland. He also was a two-time Lou Groza Star of the Week honoree for his performances in Florida State’s victories over NC State and Clemson. He was named offensive special teams player of the year for the Seminoles as selected by the Florida State coaching staff. He led the ACC in field goals per game with a career-high 2.2 field goals per game average. Gano has the highest field goal percentage in the ACC; in 2008, he made 92.3 percent of his field goal attempts (24 of 26) and led the league in field goals made with 24. He was also the ACC’s leading scorer with 105 points and a 9.5 points per game average. Gano is the only kicker in FSU history to convert over 90% of his field goals in a season. He is one of only two punters ever to be named the MVP of a bowl game, when he was named the Most Valuable Player in the 2008 Champs Sports Bowl. He holds the Seminoles single season record for 50+-yard field goals, completing five straight attempts from 50 yards or longer. Despite only kicking for one season, Gano finished second in career 50-yard field goals at FSU behind two time Lou Groza Award winner Sebastian Janikowski.

On December 8, 2009, Gano was signed by the Washington Redskins, replacing veteran Shaun Suisham. He successfully connected on his first career NFL field goal attempt, a 46-yard attempt against the Oakland Raiders on December 13, 2009. Gano continued to play for the Redskins in the 2010 season. He cemented his status as a clutch kicker for the Redskins by contributing to three overtime game-winning field goals when playing against the Green Bay Packers, Tennessee Titans, and Jacksonville Jaguars.

Due to Gano’s inconsistency in the 2010 season, the Redskins brought Shayne Graham to compete. After a good performance in the preseason and horrible performance by Graham in the first preseason game, Gano was kept on the final roster before the start of the new season. In Week 9 against the San Francisco 49ers in the 2011 season, he kicked a 59-yard field goal, which broke the Redskins’ franchise record of 57 yards. At the end of the season, he made 31 of 41 field goal attempts with five of the ten misses being blocked kicks.

On March 3, 2012, the Redskins tendered a contract with Gano establishing exclusive negotiating rights and guaranteeing him a league minimum salary. He was once again forced to compete for his job after the team signed Neil Rackers. Originally it seemed that once again, Gano kept his spot on the Redskins’ roster after Rackers was cut by the team on August 27. In a surprise transaction by the Redskins, Gano was released the next day after the team signed veteran Billy Cundiff.

On November 20, 2012, Gano was signed by the Carolina Panthers, replacing Justin Medlock. He played in the last six games of the season under head coach Ron Rivera and converted nine out of eleven field goal attempts. In the 2013 season, he converted all 42 extra point attempts and 24 of 27 field goal attempts.

On February 28, 2014, it was announced that Gano had signed a new four-year contract with the Panthers worth $12.4 million. He converted all 34 extra point attempts and 29 of 35 field goal attempts.

On November 2, 2015, Gano kicked a game-winning 52-yard field goal in overtime against the Indianapolis Colts. The successful field goal helped move the Panthers to a franchise-best 7–0 start.

Gano had an NFL-leading 62 points in November 2015, going 15-for-17 on field goals and 17-for-18 on extra-point attempts. For his performance during November, Gano was awarded the NFC Special Teams Player of the Month. He became only the second kicker in Panthers’ franchise history to win the award (the first was John Kasay in September 1996). Through the first 12 weeks of the season, Gano ranked second in NFL in points scored with 110, trailing only New England Patriots kicker, Stephen Gostkowski (111). During the Panthers 38–35 victory over the New York Giants, Gano kicked his second walk-off winner this season as time expired to move the Panthers to a 14-0 record. Gano finished the 2015 NFL season with 146 points, breaking John Kasay‘s team record for most in a season (145, 1996). During the season, he also topped the NFL with 69 touchbacks and a 72.0 yard average kickoff distance.

On September 17, 2017, in Week 2, Gano scored all of the Panthers’ points in a 9–3 victory over the Buffalo Bills. The three field goals he converted were a 34-yarder, 28-yarder, and a 20-yarder.

Gano was named to his first Pro Bowl in 2017 as an injury replacement for Greg Zuerlein.

On March 6, 2018, Gano signed a four-year, $17 million contract extension with the Panthers. On October 7, 2018, Gano kicked a 63-yard field goal game-winning field goal as time expired in a 33-31 victory over the New York Giants, earning him NFC Special Teams Player of the Week. The kick also tied the non-altitude assisted field goal record set in 1970 by Tom Dempsey and tied in 2012 by David Akers. He was placed on injured reserve on December 19, 2018 after sitting out the previous two games due to injury. He finished the season having converted 30 of 33 extra point attempts and 14 of 16 field goal attempts.

On August 30, 2019, Gano was placed on injured reserve, ending his 2019 season. He was released by the team on July 30, 2020.

Gano signed with the New York Giants on August 19, 2020.