Davis enrolled in the University of Maryland, where he majored in studio art and played for the Maryland Terrapins football team. In 2003, Davis saw the most consistent action of any true freshman, playing in all thirteen contests. He had five receptions for 87 yards (11.8 avg) and led the kickoff coverage unit with eight solo tackles.

In 2004, he played in every game, starting at H-back against Northern Illinois, Duke, Georgia Tech, Clemson, Virginia Tech, and Wake Forest. He finished second on the team with 27 catches for 441 yards and had 16.3 avg and three touchdowns.

Through Week 11 of the 2009 season, Davis led the NFL with nine touchdown receptions, tied with wide receivers Larry Fitzgerald and Randy Moss. In the final game of the season, he tied the all-time record for most touchdown receptions for a tight end in a single season with 13, sharing the record set by Antonio Gates of the San Diego Chargers in 2004; that record stood until 2011, when it was broken by Rob Gronkowski of the New England Patriots. He was also selected to appear in his first Pro Bowl.

In 2005, Davis was a Consensus All-American and All-Atlantic Coast Conference first-team selection. He was a finalist for the Mackey Award, given to the nation’s top tight end. He started every game, leading the team with 51 receptions and the conference with 871 receiving yards (17.1 avg). His six touchdown catches rank tenth on the school’s season-record list. His 51 receptions also rank tenth on Maryland’s annual record chart while his 871 yards rank fifth. He was graded 82.5% for blocking consistency as he registered 67 knockdowns, including 18 blocks down field and had eight touchdown-resulting blocks.

Davis was selected sixth overall in the first round of the 2006 NFL Draft by the San Francisco 49ers. He joined Kellen Winslow Jr. as the fourth highest tight end ever drafted after Ron Kramer, (Green Bay, fourth overall in 1957) Mike Ditka (Chicago, fifth overall in 1961), and Riley Odoms (Denver, fifth overall in 1972). He was the top tight end prospect in the 2006 NFL Draft, partially due to a strong performance at the scouting combine. He ran the 40-yard dash in 4.38 seconds. Davis also broad-jumped 10’08”, nearly a foot farther than the next-best tight end, Marcedes Lewis.

Vernon’s first reception in the NFL was a 31-yard touchdown catch from quarterback Alex Smith, against the Arizona Cardinals in Week 1 on September 10, 2006. He added a career-long 52-yard touchdown against the Green Bay Packers on December 10 with a short catch followed by a long run. Davis played in ten games in the 2006 season due an injury he suffered on September 24, 2006. He sustained a hairline fracture to his left fibula, on a non-contact play against the Philadelphia Eagles, but returned on November 19 against the Seattle Seahawks. For his rookie season, Davis had 265 yards receiving on 20 catches, averaging 13.2 yards per reception. He also had three receiving touchdowns.

During October 2008, after catching a seven-yard pass in the third quarter against the Seahawks, Davis slapped Seahawks safety Brian Russell in the facemask, resulting in a 15-yard penalty, causing head coach Mike Singletary to bench him and then send him to the locker room for the game’s remainder. After the game, Singletary then spoke his famous “I want winners” rant. This resulted in Davis changing his attitude from himself, to the team. The following game against the Cardinals, Davis leaped over a Cardinal defender and caught a pass from quarterback Shaun Hill resulting in a touchdown, his first of the season. He started all 16 regular season games, and finished the season with 31 receptions for 358 yards and two touchdowns.

Before the 2010 season, he was awarded a five-year contract extension for $37 million with $23 million guaranteed. The deal made Davis the league’s highest paid tight end. Prior to a week 3 game against the 2–0 Kansas City Chiefs, Davis guaranteed the 49ers would win. The 49ers would eventually lose 10–31. Against the Oakland Raiders in Week 6, he recorded his third straight game with a touchdown. Davis finished the season with 56 catches and 914 yards, resulting in 16.3 yards per catch.

In late 2010, Davis founded Modern Class Design (MCD) with business partner Antone Barnes. Modern Class Design is a full-service fine arts and interior design company that offers comprehensive design services for homes and commercial spaces including interiors and landscape architecture. Davis also owns a chain of Jamba Juice franchises.

During the 2012 season, Davis caught 41 passes for 548 yards and 5 touchdowns. The 49ers would eventually enter the NFC Championship for the second straight season to face off against the Atlanta Falcons at the Georgia Dome. Despite trailing 17-0, the 49ers won the NFC Championship game against the Falcons by a score of 28–24, allowing the 49ers to enter the Super Bowl for the first time in 18 years. In Super Bowl XLVII, Davis had 6 catches for 104 yards in the narrow 34-31 loss to the Baltimore Ravens.

In December 2012, Davis opened Gallery 85 on Santana Row in San Jose, California. Gallery 85 is an art gallery for new and emerging artists giving them access to high-end exposure.

Davis began the 2013 season much like the 2012 playoffs ended: as a trusted and reliable target for quarterback Colin Kaepernick, catching his first touchdown pass of the season in the first quarter of the first game, at Candlestick Park on September 8, 2013 against the Green Bay Packers. He added two touchdown receptions in the 2013 NFC Playoffs, one coming against the Green Bay Packers in a Wild Card Round victory, and another in a Divisional Round victory against the Carolina Panthers.

In October 2013, it was reported that Davis would be offering stock in his future earnings via a venture with Fantex as part of a new financial instrument being sold by Fantex. Davis planned to offer a 10% share of all future earnings from his brand marketing company to Fantex, which would then turn around and divide it into shares of a tracking stock that can be traded within their own exchange. In January 2014, the stock offering was confirmed. The proposed offering was 421,100 shares, valued at $10 per share, for a total proposed valuation worth $4.2 million.

During the 2014 season, Davis only caught 4 passes for 44 yards, and two touchdowns (both in Week 1 against the Dallas Cowboys). He was dealing with ankle and back issues, which hindered him most of the time during the season.

On November 2, 2015, Davis and a 2016 seventh-round draft pick were traded from the San Francisco 49ers to the Denver Broncos for sixth-round picks in 2016 and 2017. His first game as a member of the Broncos was against his brother Vontae and the Indianapolis Colts. With Brock Osweiler as the starting quarterback, he had four receptions for 69 yards in a 17–15 win over the Chicago Bears. He then added a combined four receptions for 35 yards in wins against the New England Patriots and San Diego Chargers. Davis had a season-high seven catches for 74 yards in a 15–12 loss to the Oakland Raiders. On February 7, 2016, Davis won his first Super Bowl championship after the Broncos defeated the Carolina Panthers by a score of 24–10 in Super Bowl 50. Despite ending the Super Bowl with no receptions, Davis made a key block downfield during a crucial 34-yard run by teammate C. J. Anderson, the longest rush of the game.

Davis made a cameo appearance in the music video for the song “Get Lo” by Ron Artest and Mike Jones. Davis made an appearance on Pretty Wild, and Whose Line is it Anyway? in 2015.

On March 31, 2016, Davis signed a one-year contract with his hometown Washington Redskins. In a Week 6 game against the Philadelphia Eagles, Davis caught his first touchdown pass in over two years, helping the Redskins win their fourth straight game of the season. Davis had started the game in replacement of an injured Jordan Reed and finished with two receptions for 50 yards and a touchdown. The following week, he earned his third start in a row and finished with six receptions for 79 receiving yards in a 17–20 loss to the Detroit Lions. On October 30, 2016, Davis caught five passes for 93 yards in a 27–27 tie with the Cincinnati Bengals. During a Week 9 matchup with the Minnesota Vikings, he caught three passes for 66 yards and caught a 38-yard touchdown reception from quarterback Kirk Cousins during the Redskins’ 26–20 victory.

On March 8, 2017, Davis signed a three-year contract extension with the Redskins. Overall, in the 2017 season, Davis finished with 43 receptions for 648 yards and three touchdowns.

In the season-opener against the Philadelphia Eagles, Davis caught 4 passes for 59 yards including a 48-yard touchdown. He was placed on injured reserve on November 22, 2019, after missing most of the season with a concussion. Davis announced his retirement via a Fox NFL skit prior to Super Bowl LIV on February 2, 2020.

In September 2020, Davis was announced as one of the celebrities competing in the 29th season of Dancing with the Stars. He partnered with Peta Murgatroyd and was the fifth couple eliminated from the competition, lasting six weeks.