Against his home town Cincinnati Bearcats he was a huge factor on defense in an overtime win with 13 total tackles and an interception.

On July 2, 2014, it was reported that starting weakside linebacker Kiko Alonso was expected to miss the entire season after tearing his ACL.

Defensive coordinator Jim Schwartz held an open competition to between Brown and Bradham to name a new starter.

[9] Head coach Doug Marrone named Brown the backup weakside linebacker to begin the season, behind Bradham.

He made his professional regular season debut and first career start in the Bills' season-opener at the Chicago Bears and recorded seven combined tackles in their 23–20 victory.

He earned the start in place of Bradham, who was suspended for their season-opener after violating the league's policy and program for substances of abuse.

[10] The following week, he started in place of Keith Rivers after he was inactive due to a groin injury he sustained in the season-opener.

Prior to Week 7, Brown supplanted Rivers as the starting strongside linebacker and remained as the starter for the last ten games of the season.

On October 26, 2014, Brown recorded nine combined tackles, a pass deflection, and made his first career interception during a 43–23 win at the New York Jets in Week 8.

He intercepted a pass by quarterback Geno Smith that was originally intended for tight end Jeff Cumberland and returned it for no gain.

[12] He finished his rookie season in 2014 with 109 combined tackles (66 solo), two pass deflections, and an interception in 16 games and 14 starts.

[14] On January 1, 2015, it was announced that Marrone opted to exercise a clause in his contract and resign from his role after finishing with a 9–7 record in 2014.

[16] Head coach Rex Ryan officially named Brown and Bradham the starting inside linebacker to begin the regular season.

On September 27, 2015, Brown made seven combined tackles, two pass deflections, two interceptions, and a touchdown in the Bills' 41–14 win at the Dolphins in Week 3.

[18] He finished his second season with 120 combined tackles (66 solo), four pass deflections, two interceptions, a forced fumble, and a touchdown in 16 games and 16 starts.

[21] On October 30, 2016, Brown recorded eight combined tackles and made his first career sack on quarterback Tom Brady during a 31–25 loss to the Patriots in Week 8.

[24] On November 19, 2017, Brown collected 13 combined tackles (11 solo) in the Bills' 54–24 loss at the Los Angeles Chargers in Week 11.

[25] He finished his last season with the Bills with a career-high 144 combined tackles (84 solo) and three pass deflections in 16 games and 16 starts.