[28] The first transactions of the year occurred shortly after the conclusion of the 2015 regular season on January 4, 2016, when the Bears signed cornerback De'Vante Bausby, quarterback Matt Blanchard, center Cornelius Edison, fullback Paul Lasike, wide receivers Marcus Lucas and Nathan Palmer, linebacker Danny Mason, tight end Gannon Sinclair and guard Martin Wallace to reserve/futures contracts.

[14] A week later, on March 16, defensive end Jarvis Jenkins also joined the Jets,[17] while linebackers Shea McClellin and LaRoy Reynolds signed with the Patriots and Atlanta Falcons, respectively.

[79] In the preseason opener against the Broncos, the Bears fell behind early when Mark Sanchez threw a 32-yard touchdown pass to Demaryius Thomas, who beat cornerback Bryce Callahan for the score.

The Broncos got the ball back on the next drive[81] when Lorenzo Doss intercepted Brian Hoyer, and came close to scoring once again on McManus' 48-yard field goal, but Chris Prosinski blocked the kick.

Gould kicked a 36-yard field goal to close the margin; Connor Shaw replaced Hoyer for the final drive, throwing a 22-yard touchdown pass to B. J. Daniels as time expired.

[84] Chicago had two opportunities during the second half, but Gould missed a 48-yard field goal wide left and the offense was unable to capitalize on Deiondre' Hall's interception of Aaron Murray, turning the ball on downs.

[93] On offense, the Bears faced a Texans defense that was ranked third in the NFL in 2015, which WBBM-TV writer Jeff Joniak wrote should be handled by controlling the ball and blocking defenders J. J. Watt, Whitney Mercilus and Jadeveon Clowney.

[101] Though the Bears attempted to respond with Connor Barth's 31-yard kick, it hit the left upright; they would take the lead on their next series with Jeremy Langford's one-yard touchdown run, receiving support from Jay Cutler throwing a 49-yard pass to Alshon Jeffery to reach the Eagles' five-yard line.

The Bears also struggled with injuries during the game, with seven players exiting as a result: Cutler (thumb), Lamarr Houston (knee), Eddie Goldman (ankle), Adrian Amos,[102] Bryce Callahan and Chris Prosinski (concussions), and Ka'Deem Carey (hamstring).

The defense, also depleted by injuries with players like Danny Trevathan and Eddie Goldman ruled out for the game,[106] had to be able to successfully tackle Cowboys receiver Dez Bryant and tight end Jason Witten while also applying pressure on rookie quarterback Dak Prescott.

Against a Detroit offense led by quarterback Matthew Stafford, the Bears needed to contain his targets like Marvin Jones, who had excelled over the course of the 2016 season, Pro Bowler Golden Tate, the experienced Anquan Boldin and young tight end Eric Ebron.

[122] The Bears escaped a 7–0 deficit when Tracy Porter intercepted Bortles in the endzone[123] to stop an 84-yard drive, instead taking a three-point lead on Connor Barth's 36-yard field goal in the second quarter.

The Jaguars responded with Ivory's one-yard touchdown run in the fourth quarter; after a Chicago punt, they reclaimed possession when Willie Young stripped the ball from Bortles and Akiem Hicks recovered the fumble.

[133] Minnesota came close to scoring a touchdown on the following series, including reaching as far as Chicago's two-yard line, but Bradford was sacked by Akiem Hicks on third down;[132] the Vikings were forced to settle for Blair Walsh's 30-yard field goal.

[133] With 5:41 left in the game, Bradford threw a 25-yard touchdown pass to Stefon Diggs to cut the margin to ten points,[132] but the Bears offense consumed much of the time remaining.

[135] The Bears and Bucs exchanged punts on their opening drives before the first turnover of the game[136] was committed when Jay Cutler's pass for Alshon Jeffery was intercepted by Brent Grimes.

[137] Though Tampa Bay was forced to punt on the following drive, they scored when former Bears safety Chris Conte intercepted Cutler's pass to Logan Paulsen and returned it for a touchdown.

The Bears eventually scored on Connor Barth's 54-yard field goal and regained the ball when Winston's pass for Cecil Shorts was deflected and intercepted by Harold Jones-Quartey.

[137] Chicago took advantage of the turnover to reach as close as Tampa's four-yard line, but Cutler was sacked by Noah Spence and fumbled, Kwon Alexander recovering the ball for the Bucs.

Cameron Brate caught a ten-yard touchdown pass from Winston on the ensuing drive to make the score 14–3, followed by Roberto Aguayo kicking a 30-yard field goal to force a two-touchdown margin.

[137] The Bears also lost Kyle Long to an ankle injury during the game when Paul Lasike landed on his right foot while attempting to catch an errant screen pass; he was eventually placed on injured reserve.

"[140] On the opening drive, Jay Cutler threw a 19-yard touchdown pass to Zach Miller, but in windy conditions, Connor Barth missed the extra point wide right.

[141] The Giants responded with Rashad Jennings' two-yard touchdown run, though former Bear Robbie Gould also missed the extra point when his kick hit the left upright.

[149] With Jay Cutler sidelined,[150] Matt Barkley made his first career NFL start against a Dick LeBeau-led defense that blitzed often; on second down, the Titans recorded 12 sacks, second-most in the league.

For the Bears defense, they faced an offense powered by a running game featuring DeMarco Murray and Derrick Henry, while quarterback Marcus Mariota led a unit that ranked eighth in the NFL in five-minute drives and a fifth-ranked third down conversion rate.

Matt Barkley, who played in rowdy stadiums during his college career at USC, faced a Ford Field that Jeff Joniak stated would be agitated by the Lions' recent success, describing the atmospheres as "just different in the NFL."

Connor Barth kicked a 26-yard field goal and the Bears took the lead later in the second quarter when Matt Barkley threw a ten-yard touchdown pass to Josh Bellamy.

[171] Thompson ran for a 17-yard touchdown on the next drive;[172] when Chicago entered Washington territory once again, Barkley's pass for Josh Bellamy went into triple coverage and was intercepted by Bashaud Breeland at the one-yard line.

[174] Both teams punted on their next drives before the Bears scored for the first time in the game;[175] Langford took the snap before handing the ball off to Cameron Meredith, who passed to Barkley for the two-yard touchdown.

[191] However, right guard Kyle Long suffered an ankle injury in week ten and was placed on injured reserve,[138] while center Hroniss Grasu tore his ACL during the offseason and did not play in 2016.