Collins was born in McCall Creek, Mississippi. He attended Franklin County High School in Meadville, Mississippi, where he played high school football for the Franklin County Bulldogs. He first played as a quarterback, receiver and safety before concluding his career as a quarterback and outside linebacker. He led the team to the Class 3A State Championship during his first year at quarterback, accounting for over 2,000 yards of offense and 26 touchdowns for the 2006 season. As a senior in 2007, he had over 1,200 yards rushing and 1,000 yards passing while leading his team to the state championship game. He was selected to play in the Mississippi-Alabama All-Star game, where he recorded a solo tackle.
Also a standout track and field athlete, Collins was a state track qualifier. At the 2009 3A South State Meet, he earned first-place finishes in the shot put (51-6) and discus throw (156-0 or 47.80m), while also placing second in both the high jump (6-4 or 1.93m) and triple jump (43-10.5) events. He captured the 2009 MHSAA (Mississippi High School Athletics Association) 3A shot put title with a throw of 15.90 meters (52-1), and also took third in the triple jump after recording a career-best leap of 13.58m (44-5.25).
A three-star athlete by Rivals.com, Collins was ranked No. 68 at that position in the country and No. 21 overall in the state of Mississippi. He was a three-star prospect by Scout.com. He was named 1st team All-State by The Clarion-Ledger. He was Max Lemming's of MaxPreps.com's No. 12 combo passer in the country.
Collins enrolled in the University of Southern Mississippi, and played for the Southern Miss Golden Eagles football team from 2009 to 2012. He played defensive back, defensive end and linebacker. During his college career, he compiled 314 tackles, 21 quarterback sacks, three interceptions and three touchdowns. He was a first-team All-Conference USA selection following his senior season in 2012.
Collins' broad jump, at 11' 7", set an NFL Combine record for all positions. The record was broken in 2015 by cornerback Byron Jones, but remains the record for linebackers.
The New England Patriots selected Collins with their first pick in the 2013 NFL Draft, the 52nd overall pick in the second round. Collins's rookie campaign was relatively quiet, recording few defensive statistics while being a force on special teams. He had a breakout game on January 11, 2014 in the divisional round of the NFL playoffs against the Indianapolis Colts racking up 6 tackles, 1 QB sack, and 1 interception.
The 2014 season proved to be a breakout year for Collins. For the season, he recorded 116 tackles, 4.0 sacks, 2 interceptions, and 4 forced fumbles. He started all 15 games that he played. On February 1, Collins and the Patriots won Super Bowl XLIX against the Seattle Seahawks 28-24.
On October 18, 2015, Collins made one of the most athletic plays of his career. With the Patriots ahead by seven points with 1:19 to go in the fourth quarter, Collins took a running start and leapt over the entire Colts' offensive line and blocked the extra point attempt. On November 6, 2015, Collins was diagnosed with an undisclosed illness. Collins was inactive for the next four games (Weeks 9–12). On December 4, 2015, Collins confirmed he recovered from the illness. He returned to action on December 6, recording eight tackles and forcing a fumble in a 35-28 loss to the Philadelphia Eagles. Collins scored his first career touchdown in a Week 16 loss to the New York Jets, returning a Jabaal Sheard-forced fumble 14 yards.
On December 22, Collins was named to his first Pro Bowl. He was selected to the 2015 AP All-Pro second team at outside linebacker, finishing fourth at that position with eight votes; he also received two votes at inside linebacker.
On October 31, 2016, Collins was traded to the Cleveland Browns for a conditional 2017 third round draft pick. In his first game as a Brown in Week 9 against the Dallas Cowboys, Collins had 8 total tackles in a 35-10 loss.
On January 23, 2017, Collins signed a four-year, $50 million contract with the Browns.