Goodwin was a two-time NCAA champion in the long jump (2010, 2012) and a four-time All-American in track and field. He won five Big 12 Conference championships and made the All-Big 12 team seven times. He is the Longhorns' indoor record holder in the long jump and was the runner-up for the 2012 NCAA Indoor long jump title.
In his collegiate career, Goodwin started 21 of the 49 games in which he appeared, including the 2010 BCS National Championship Game against Alabama. His final career statistics included 116 receptions for 1,296 yards and six touchdowns, 45 times for 341 yards and 44 kickoff returns for 985 yards and one touchdown. He also returned a punt for 22 yards. Some of his key plays include his first touchdown of his 2009 freshman year, a game-winning touchdown in a 16-13 victory over the Oklahoma Sooners. Goodwin also returned a kickoff 95 yards for a touchdown to seal the Longhorns' win over the Texas A&M Aggies.
In the 2010 season, Goodwin had 31 receptions for 324 yards and one touchdown. In the 2011 season, he had 33 receptions for 421 yards and two touchdowns. In the 2012 season, Goodwin was named a semifinalist for the Campbell Trophy. In the 2012 Alamo Bowl against Oregon State, Goodwin rushed for a 64-yard touchdown, and caught the game-winning, 36-yard touchdown pass—an effort that was good enough to earn him the game's Offensive Most Valuable Player trophy. In the 2012 season, he had 26 receptions for 340 receiving yards and three receiving touchdowns.
After posting the third-fastest 40-yard dash time ever at the NFL scouting combine, Goodwin was drafted by the Buffalo Bills in the third round, with the 78th overall pick, of the 2013 NFL Draft.
On May 10, 2013, Goodwin signed a four-year contract with the Bills, where he also practiced in his first day of rookie minicamp. He caught his first career touchdown Week 6 against the Cincinnati Bengals, a 40-yard pass from Thaddeus Lewis. Goodwin played 12 games in his rookie season making 17 receptions for 283 receiving yards. He also had 16 kickoff return opportunities totaling 351 returning yards.
In 2014, hobbled by numerous injuries (concussion, ankle, ribs, and hamstring), Goodwin caught only one pass for 42 yards, which came against the Detroit Lions.
After missing five games with broken ribs, Goodwin posted two receptions for 24 yards in the 2015 season.
In 2016, Goodwin posted 29 receptions, 431 yards, and three touchdowns, setting career highs in games played, receptions, and receiving yards. While Goodwin enjoyed his most productive season, he was also inconsistent. His 42.6% catch rate ranked 107th among qualified NFL wide receivers in 2016.
On March 9, 2017, Goodwin signed a two-year contract with the San Francisco 49ers. On September 10, 2017, in his 49ers debut, Goodwin had three receptions for 21 yards in the season opening 23–3 loss to the Carolina Panthers. On November 12, 2017, against the New York Giants, he caught his first touchdown of the season on an 83-yard reception. After beating one defender, Goodwin blew a kiss to the sky and once in the end zone, then took a knee in prayer before falling to both knees with his head in hands, as his teammates gathered around him. After the game, in which the 49ers beat the New York Giants for their first win of the season, Goodwin revealed that he and his wife had lost their prematurely born son due to complications during pregnancy in the early morning hours the day of the game. In Week 15, Goodwin caught a career-high 10 passes for 114 yards in a 25-23 win over the Titans. Goodwin established new career highs in receptions and receiving yards in his first season with the 49ers, finishing the season with 56 catches for 962 yards and two touchdowns.
On March 8, 2018, Goodwin signed a three-year, $20.3 million contract extension with the 49ers that will last through the 2021 season.
In Week 6, against the Green Bay Packers, Goodwin set career-highs with 126 receiving yards and two receiving touchdowns. In the 2018 season, he finished with 23 receptions for 395 receiving yards and four receiving touchdowns.
Goodwin made the 2012 United States Olympic team in the long jump with a career-best and meet-best mark of 8.33m (27-04.25) at the US Olympic Team Trials, a jump that would have been good enough to win the gold medal at the following Olympics.
At the 2012 Summer Olympics, he qualified for the finals on his first jump of 8.11m (26-7), but he failed to match that performance in the finals and finished in 10th place.
In 2015, after a three-year absence, he returned to track and field. In his first event back, despite jumping a career best 8.37m (27-05.5), he finished in fourth place, just missing qualification for the World Championship. A month later, at the 2015 Pan Am Games, he earned a silver medal with a jump of 8.27m (27-1)
In 2016, Goodwin won the long jump at the Rod McCravy Invitational in Kentucky and placed third in the Millrose Games in New York. In New York he also placed 6th in the 60m dash, with a then career best 6.68s. In March, he placed third at the United States Indoor Track and Field Championships while also making it to the semifinals in the 60-meter dash with another personal best. He won the long jump at the Meeting Region Guadeloupe with a personal best mark of Template:T&Fcalc, also a world-leading mark at the time of the meet. As of 2017, his personal best ranks him as the 43rd best long jumper of all time. Then a month later, he won the long jump at the IAAF Diamond League meet in Birmingham, England. However, his dream of returning to the Olympics came up short when he finished a disappointing seventh at the Olympic Trials in July. His best jump of 8.25m was well below his best jumps of the year, which would have been enough to qualify.