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Lock was selected by the Denver Broncos in the second round (42nd overall) of the 2019 NFL Draft. He suffered a thumb injury in the preseason and was placed on injured reserve on September 1, 2019. He was designated for return from injured reserve on November 12, 2019, and began practicing with the team again.

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. He threw for 134 yards, two touchdowns, and one interception, and he moved the Broncos down the field in the last 15 seconds (via a pass interference penalty on the Chargers' Casey Heyward Jr.) to set up a Brandon McManus 53-yard field goal as time expired, leading the Broncos to a 23–20 win, his first NFL victory. During Week 14 against the Houston Texans, a game in which the Texans were favored by nine points, Lock threw three touchdowns in the first half and led another scoring drive to start the second half, giving his team a 38–3 lead. The Broncos eventually won the game 38–24 and Lock finished with 309 passing yards, three touchdowns, and an interception. Lock ended up starting the remainder of the season. In five games, he finished with 1,020 passing yards, seven touchdowns, and three interceptions. Lock went 4-1 as a starter in 2019 and in the process, tied with legendary Broncos quarterback John Elway for the most franchise wins by a rookie QB with 4, needing only 5 games to accomplish the feat whereas Elway didn't reach the milestone until his 10th game.

In the 2017 season, Lock led the NCAA (FBS) and set the SEC and Missouri record for passing touchdowns (44) while helping the Tigers reach a bowl game after starting the season 1-5. He finished the season with 242-of-419 passing (57.8%) for 3,964 yards with 44 touchdowns and 13 interceptions (165.7 rtg.). Lock was selected to the First-team All-SEC. He finished his college football career with a total of 99 touchdowns.

He finished the 2016 regular season ranked first in the SEC in passing yards (3,399) and second in passing yards per game (283.3) and yards per completion (14.34) while posted top-20 marks nationally in all three categories as well, peaking at 10th nationally with his 3,399 passing yards. Also ranked second in the SEC in completions per game (19.75) and third in total offense (293.5). His 3,399 yards through the air are the fifth-most in program history in a single season and the most ever in a 12-game season at Mizzou, while his 23 passing touchdowns were the sixth-most in program history and only three Mizzou quarterbacks have thrown for more in a single season. He 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. Tossed for three more touchdowns on 23-of-38 passing in Mizzou's 28–27 loss to Georgia. His passing total of 1,106 yards was more than any Mizzou quarterback in his first three games ever. Played only the first half against Delaware State, but put up huge numbers in the 79–0 win. In the first half alone, he completed 26-of-36 passes for 402 yards while matching the school record with five touchdowns. He closed his season by sparking a second-half, 17-point comeback with a 67-yard TD pass to Johnathon Johnson against Arkansas. He finished that game going 16-for-26 with 268 yards and a score.

Lock began his collegiate career by going 6-for-10 for 138 yards and a touchdown in the season-opener against Southeast Missouri State while coming off the bench for two series. He then took over as Mizzou's starting quarterback over the final eight games of 2015. In a win over South Carolina, he became the first Mizzou true freshman to start at QB since Corby Jones in 1995, going 21-for-28 for 136 yards and a pair of touchdowns. Against BYU at Arrowhead Stadium, Lock was 19-of-28 for a career-best 244 yards and a touchdown while also setting career-highs in both passer rating and passing yards while posting his second-best completion percentage of the season. He finished the season 129-of-263 for 1,332 yards and four touchdowns.

Lock attended Lee's Summit High School in Lee's Summit, Missouri. As a junior, he passed for 3,060 yards and 35 touchdowns. As a senior in 2014, he was the Kansas City Star's All-Metro Player of the Year after passing for 2,731 yards and 28 touchdowns. Lock was rated by Rivals as a four-star recruit and was ranked as the sixth-best pro-style quarterback in the 2015 class. Lock committed to the University of Missouri to play college football. He was also considered a two-star basketball prospect as a shooting guard, but he retired from basketball after high school.

Drew Lock (born November 10, 1996) is an American football quarterback for the Denver Broncos of the National Football League (NFL). He played college football for the Missouri Tigers and was drafted by the Broncos in the second round of the 2019 NFL Draft.