He played college football for the Missouri Tigers and was selected by the Denver Broncos in the second round of the 2019 NFL draft.

[5] Lock began his collegiate career by going 6-for-10 for 138 yards and a touchdown in the 2015 season-opener against Southeast Missouri State while coming off the bench for two series.

[7] In a 24–10 win over South Carolina, he became the school's first true freshman to start at quarterback since Corby Jones in 1995,[8] going 21-for-28 for 136 yards and a pair of touchdowns.

[7] In Missouri's second game of the 2016 season, Lock completed 24-for-37 for a career-high 450 yards while tying a school record with five touchdowns against Eastern Michigan in Mizzou's home opener.

[19] On October 21, against Idaho, he had 467 passing yards, six touchdowns, and one interception to break a five-game losing streak for Missouri.

[26] Lock helped lead Missouri to a 3–0 start with 11 passing touchdowns and one interception in the stretch against UT Martin, Wyoming, and Purdue.

On November 30, 2019, the Broncos activated Lock off of injured reserve and named him the starter for their game the next day against the Los Angeles Chargers.

[44] In Week 1 against the Tennessee Titans on Monday Night Football, Lock threw for 216 yards and a touchdown during the 16–14 loss.

[50] In Week 10 against the Las Vegas Raiders, Lock had the worst passing performance of his career, throwing for 257 yards, one touchdown, and 4 interceptions in a 37–12 loss.

[51] On November 28, 2020, Lock was placed on the reserve/COVID-19 list after coming in close contact with Jeff Driskel, who tested positive for the virus.

On August 25, Bridgewater was named the starter for week 1[59] ahead of Lock, after a close battle in the first and second preseason games.

[60][61] In Week 12, Lock entered the game against the Chargers late in the first half after a leg injury temporarily sidelined Bridgewater.

[69] Upon arriving in Seattle, Lock changed his jersey number from #3, which he had worn in Denver and at Missouri, to #2, telling reporters he did so both out of respect for Wilson, who wore #3, and out of a desire to "write my own story.

[75][76] Lock played poorly, completing 2-of-6 passes, including a critical interception to Rams' cornerback Derion Kendrick, which ultimately lost the game for the Seahawks.

[77][78][79] In Week 14, against the San Francisco 49ers, Lock had his first start since being traded to Seattle, due to Smith suffering a groin injury.

[80] Although Smith was active for the Week 15 game against the Philadelphia Eagles, he had not recovered enough to start, making Lock the starter again.

[83] Once thought to be competing with Daniel Jones for the starting quarterback job, Lock asserted that he was brought in to be a backup.

[84] Lock was named the starter for the Giants' Week 13 Thanksgiving matchup against the Dallas Cowboys, following the release of Jones and an injury to Tommy DeVito.

[85] In Week 17 against the Indianapolis Colts, Lock accounted for all five of the Giants' offensive touchdowns, posting a career-high passer rating of 155.3 with no turnovers in a 45–33 victory.