In the 2011–12 NFL playoffs with the 49ers, Davis caught the game-winning touchdown pass from Alex Smith against the New Orleans Saints, referred to as "the Catch III".

At Dunbar, he was teammates with future Cleveland Browns kick return specialist and wide receiver, Josh Cribbs.

In his senior season, Davis caught 21 passes for 511 yards and five touchdowns, despite missing three games with a deep bone bruise below his knee.

Davis was the top tight end prospect in the 2006 NFL Draft, partially due to a strong performance at the scouting combine.

[18] Smith 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 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.

[22] In 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 Davis and then send him to the locker room for the rest of the game.

In the next game against the Arizona Cardinals, Davis leaped over a defender and caught a pass from quarterback Shaun Hill resulting in a touchdown, his first of the season.

[23] Through Week 11 of the 2009 season, Davis led the NFL with nine touchdown receptions, tied with wide receivers Larry Fitzgerald and Randy Moss.

[25][26] Davis was selected to appear in his first Pro Bowl after recording 78 receptions for 965 yards and 13 touchdowns in 16 games and starts.

[31] In 2011, Davis had 67 receptions for 792 yards with six touchdowns in 16 games and starts, helping the 49ers win the NFC West division and make the postseason for the first time since 2002.

[33] Davis scored two touchdowns, and on the game-winning drive, he had a critical 47-yard reception that put the 49ers in a position to tie the game.

With nine seconds remaining, Davis caught the game-winning touchdown pass from Alex Smith, now referred to as "Vernon Post".

[34] Davis caught three passes for 112 yards and another two touchdowns against the New York Giants in the NFC Championship, but the 49ers lost 20–17 in overtime.

[37] During the NFC Championship Game, Davis recorded five receptions for 106 yards and a touchdown in the 28–24 comeback victory over the Atlanta Falcons.

With Brock Osweiler as the starting quarterback, Davis had four receptions for 69 yards during a narrow Week 11 17–15 road victory over the Chicago Bears.

[54] Despite ending the Super Bowl with no receptions,[55] Davis made a key block downfield during a crucial 34-yard run by teammate C. J. Anderson, the longest rush of the game.

[58] During a Week 6 27–20 victory over the Philadelphia Eagles, Davis caught his first touchdown since 2014, 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 the aforementioned touchdown.

[59] The following week, he earned his third start in a row and finished with six receptions for 79 yards in a 17–20 road loss to the Detroit Lions.

[69] Davis announced his retirement via a Fox NFL skit prior to Super Bowl LIV on February 2, 2020.

[74] In late 2010, Davis founded Modern Class Design (MCD) with business partner Antone Barnes.

[79] In 2013, Davis made a cameo appearance in the music video for the song "Get Lo" by Ron Artest and Mike Jones.

[83] Davis hosted the reunion and behind-the scenes special for MTV's The Challenge: Total Madness, both of which aired in July 2020.

In 2022, it was announced that Davis would star in the comedy film Plan B, alongside Jon Heder, Tom Berenger, and Shannon Elizabeth.