When Taylor graduated from Hampton in 2007, he was rated as the No. 1 dual-threat quarterback at Rivals.com. ESPN.com rated him the No. 3 overall quarterback, while Scout.com said he’s the nation’s seventh-best passer. Taylor, who is 6’1″ and 200 pounds, ran a 4.55-second 40-yard dash.

Taylor’s first action of college football came in the game against the LSU Tigers on September 8, 2007. In that game, Taylor completed 7-of-18 passes for 62 yards, rushed for 44 yards on nine attempts including his first collegiate touchdown. After that game, Tyrod was named the starter by head coach Frank Beamer. In his first collegiate start against Ohio, Tyrod threw for 287 yards, adding a rushing touchdown.

After starting every game of the 2008 season leading up to the Florida State game on October 25, Taylor suffered a high ankle sprain on the first play of the Florida State game. Sean Glennon relieved Taylor at the quarterback position after this setback. While Glennon got the start versus Miami, Taylor split time with Glennon and led a crucial fourth quarter to make it a two-point game 16–14. However, he was sacked in a crucial 4th and 3 with less than two minutes to go. After the loss, Taylor started against Duke. After committing five turnovers in the first half, he was pulled from the game and replaced by Sean Glennon. Taylor then started next week at Virginia. He performed well including a 73-yard run. He was 12-for-18 for 137 yards and one touchdown while rushing 16 times for 137 yards. He then started in the ACC Championship Game win over Boston College and was named the ACC Championship Game MVP. On January 1, 2009, he led the Hokies to a 20–7 victory over the Cincinnati Bearcats in the 2009 Orange Bowl. Overall, he finished his sophomore season with 1,036 passing yards with two touchdowns and seven interceptions.

During his junior season, Taylor led the Hokies to a 9–3 regular season record and a 2nd-place finish in the Coastal Division of the ACC. The Hokies played the Tennessee Volunteers in the 2009 Chick-fil-A Bowl and won 37–14, finishing with a final record of 10–3. After climbing as high as #4 in the rankings, Tech lost back to back games against Georgia Tech and North Carolina, but finished the season ranked 10th in both the AP and USA Today Top 25 polls. In the 2009 season, he finished with 2,311 passing yards, 13 touchdowns, and five interceptions. After his junior season, he had a 23–5 career record at Virginia Tech, which was the second most wins of all time for a starting quarterback at Virginia Tech.

Taylor’s senior season began with two heartbreaking losses to Boise State at FedExField and at home to Division I-FCS James Madison. Taylor was 15-of-22 for 186 yards and two touchdowns, along with 73 yards on the ground, against Boise State, but was unable to respond following a Broncos score with 1:03 remaining. However, Taylor ultimately led the Hokies to a remarkable turnaround season, winning 11 consecutive games after the 0–2 start. The 2010 Hokies became the first ACC team to finish with an undefeated 8–0 record in ACC play in 10 years. They became ACC Champions for the fourth time in seven seasons with a 44–33 win over Florida State in the 2010 ACC Championship Game in Charlotte. Overall, in his final collegiate season, he had 2,743 passing yards, 24 touchdowns, and five interceptions. Taylor finished the regular season as ACC Player of the Year and ACC Championship Game Most Valuable Player.

Taylor participated in the 2011 East-West Shrine Game. He completed four of his five passes for 59 yards.

Taylor was drafted in the sixth round with the 180th overall pick by the Baltimore Ravens in the 2011 NFL Draft. He was the 11th quarterback to be selected that year. The Ravens previously acquired the pick from the St. Louis Rams in a trade that sent Mark Clayton to St. Louis. The Ravens played him at quarterback in spite of the fact many of the other 31 teams believed he would better be suited at wide receiver instead.

Taylor played in his first regular season game on December 4, 2011 in a victory over the Cleveland Browns. He rushed for a two-yard gain. He appeared on December 18 and threw his first-ever regular season pass, an 18-yard touchdown. He also lined up as a wide receiver for one play against the Indianapolis Colts.

On December 30, 2012, Flacco was rested for most of the Week 17 game against the Cincinnati Bengals, offering Taylor significant playing time. Taylor scored his first career touchdown on a one-yard bootleg in the fourth quarter. However, Taylor also threw a crucial interception to defensive end Carlos Dunlap, which Dunlap returned for a touchdown. The Ravens lost the game against the Bengals by a score of 23–17. Taylor, as a backup, went on to earn a championship ring when the Ravens eventually won Super Bowl XLVII over the San Francisco 49ers.

Taylor had a decent preseason in 2013 when he completed 21-of-36 passes for 263 yards and four touchdowns with two interceptions. He also showed his versatility as a runner using designed runs and scrambles while rushing for 66 yards on 15 carries. His strong preseason performance allowed him to keep his job as the Ravens backup quarterback for the third straight season.

Taylor did not see any action in the 2013 season until Week 10, in a win against the Cincinnati Bengals. He ran an end-around handoff from Flacco for a gain of 18 yards, which was the longest run by any Ravens player in that game. In Week 12 against the New York Jets, Taylor played 12 total snaps, five at quarterback. He gained seven yards on four carries though he did have a 17-yard first down run in the first quarter. His total yardage was brought down by two second half runs where he lost 13 yards. He also had one reception for six yards. On December 22, 2013, Taylor would enter the game for Flacco during a blowout loss to the New England Patriots. On his very first snap, Gino Gradkowski snapped it too far to the right, and was recovered by New England for a touchdown. He finished the 41–7 loss, completing 1-of-4 passes for two yards and an interception that the Patriots defense returned for a touchdown.

Taylor’s only action in the 2014 season was during a Week 6 48–17 blowout victory over the Tampa Bay Buccaneers. Taylor came in during the fourth quarter to relieve Flacco.

On March 12, 2015, Taylor signed a three-year, $3.35 million contract with the Buffalo Bills. On August 31, 2015, Taylor was named starting quarterback of the Bills for the 2015 season by head coach Rex Ryan, beating out former Bills first round pick EJ Manuel and veteran Matt Cassel after a preseason quarterback competition among the three candidates.

Taylor entered training camp as the starting quarterback for the Bills in the final year of his original Bills contract, as the third year of his deal was voided when he played more than 50% of the snaps in the 2015 season. On August 12, 2016, Taylor signed a six-year contract extension worth $92 million with the Bills. The contract contained an option after the first year, however. On Christmas Eve, against the Miami Dolphins, he passed for a career-high 329 yards and three touchdowns in the 34–31 overtime loss. Taylor completed 269-of-436 passes for 3,023 yards and 17 touchdowns with six interceptions in the 2016 season. In addition, he rushed for 580 yards and six touchdowns. He was made inactive for the final game of the season due to a clause in his contract that would make his 2017 salary guaranteed if he suffered a serious injury. At the time of the game, he already had a groin injury that could require surgery. On January 5, 2017, Taylor had surgery to repair a core muscle issue. Taylor was selected as a 2017 Pro Bowl alternate, but he declined the invitation due to injury.

On January 25, 2016, Taylor and teammate center Eric Wood were selected to the Pro Bowl. They replaced Panthers quarterback Cam Newton and Panthers center Ryan Kalil, who were playing in Super Bowl 50. In the Pro Bowl, Taylor completed 8-of-14 passes for 120 yards and a touchdown, but he also threw three interceptions.

On March 9, 2018, the Bills agreed to trade Taylor to the Cleveland Browns for a 2018 third-round draft pick. The deal became official five days later, on March 14, at the start of the NFL year.

Despite drafting quarterback Baker Mayfield first overall in the 2018 NFL Draft, the Browns committed to Taylor as their season starter. In his first start against the Pittsburgh Steelers, Taylor helped the Browns snap a 17-game losing streak dating back to 2016, but the game ended in a 21–21 tie. Taylor completed 15 of 40 pass attempts for 197 yards, a touchdown, and an interception while also rushing for 77 yards and a touchdown.

Taylor was injured in Week 3 during a Thursday Night Football game against the New York Jets, which prompted Mayfield to take over at quarterback en route to the Browns finally winning their first game since 2016. Taylor appeared in only one other game in the 2018 season, completing an 11-yard pass against the Kansas City Chiefs in Week 9.

On March 13, 2019, Taylor signed a two-year, $11 million contract with the Los Angeles Chargers, reuniting with former offensive coordinator and one-time interim head coach Anthony Lynn. In Week 14, in the 45–10 victory over the Jacksonville Jaguars, Taylor came into the game in relief of Philip Rivers and threw a 14-yard touchdown pass to Virgil Green.

Taylor lists Steve Young, Warren Moon, Michael Vick, and Allen Iverson as his biggest athletic inspirations. He is a Christian, having been raised in the faith by his parents. In 2020, Taylor made a $25,000 contribution via his foundation to the Virginia Peninsula Foodbank during the COVID-19 pandemic.