A native of Homestead, Florida, Brown attended Homestead High School where he was named an All-Dade County selection as a senior in 2007.
In 2008, Brown enrolled at Mars Hill College in Mars Hill, North Carolina. Brown was named the SAC Freshman of the Year, after catching 27 passes for 619 yards and seven touchdowns while leading the team with 1,472 all-purpose yards. He sat out the 2009 season before transferring to Coffeyville Community College in 2010. He didn’t play as he was redshirted.
After the season, Brown decided to transfer to Pittsburg State University. In 2011, he was a second-team AP Little All-American as all-purpose player while leading the Gorillas to the NCAA Division II National Championship. He was named first-team All-MIAA as kick returner and second-team All-MIAA as a wide receiver after he led his team with 61 receptions for 1,216 yards and 12 touchdowns. In 2012, he was named a first-team AP Little All-American as an all-purpose player, and first-team All-MIAA as kick returner and wide receiver. He was named the MIAA and the NCAA Division II National Special Teams Player of the Year. Brown started 10 games and led team with 63 receptions for 973 yards and eight touchdowns. In 2013, he was named 2013 MIAA Special Teams Player of the Year as well as the NCAA Division II National Special Teams Player of the Year. He was also named a second-team AP Little All-American as all-purpose player and first-team All-MIAA player as kick returner and wide receiver. He caught 61 passes for 1,198 yards and 14 touchdowns.
He finished as Pitt State’s all-time leader in receptions (185), receiving yards (3,380) and receiving touchdowns (34). His 3,380 receiving yards ranks fifth in MIAA history. Between receiving, rushing and return yards, Brown finished his career with 7,716 all-purpose yards, 6,244 at Pitt State.
He was drafted by the Arizona Cardinals in the third round (91st overall) of the 2014 NFL Draft. Brown was the first Pittsburg State Gorilla drafted since Ronald Moore in 1993.
In his debut for the Arizona Cardinals, Brown caught his first professional touchdown on a 13-yard pass from Carson Palmer against the San Diego Chargers in Week 1 of the 2014 season. He followed that performance with his first multi-touchdown game two weeks later against the San Francisco 49ers. On October 26, 2014, he caught a 75-yard game-winning touchdown pass to beat the Philadelphia Eagles. In Week 10 of the 2014 NFL season, John Brown became the first rookie in NFL history to have 4-game-winning touchdowns in a season. Brown finished the season with 48 receptions on 103 targets for 696 yards and five touchdowns.
On January 3, 2015, in the NFC Wild Card game against the Carolina Panthers, on the game's final offensive play, Brown was the final recipient of a multiple lateral play which lost 20 yards. The loss caused the Cardinals to finish the game with just 78 total offensive yards, the lowest total in NFL playoff history which broke a 56-year-old league record. Brown concluded the regular season with 65 receptions on 101 targets for 1,003 yards and seven touchdowns.
Plagued with hamstrings issues throughout the season, Brown posted 39 receptions on 72 targets for 517 yards and two touchdowns in 2016.
Brown’s nickname is Smokey and he considers it much more than a nickname, as all his family and friends refer to him as Smokey. The nickname was bestowed upon him at birth by the boyfriend of his grandmother. “He nicknamed me Smokey because when I first came out, I was blacker than what I am now,” Brown said, referring to his skin color. “Most people are like, ‘Why they call you Smokey? Because you are fast?’ But no.”