Belt enrolled at San Jacinto College in order to preserve his ability to negotiate with Boston, but eventually chose not to sign. He pitched for San Jacinto’s baseball team in 2007 and was drafted in the 11th round (348th overall) of the 2007 Major League Baseball draft by the Atlanta Braves, but again chose not to sign.

Belt transferred to the University of Texas, where he played college baseball for the Texas Longhorns for two years. In his 2008 sophomore season, Belt batted .319 with six home runs and a team-high 65 RBI while also pitching in 16 games as a reliever. After the 2008 season, he played collegiate summer baseball with the Harwich Mariners of the Cape Cod Baseball League. As a junior, Belt transitioned to first base due to shoulder problems. In 2009, during his junior season, Belt batted .323 in 63 games (76-for-235) with eight home runs, 43 RBI, and 15 stolen bases, while recording a .989 fielding percentage as part of the Texas team that finished as runners-up in the College World Series.

The San Francisco Giants selected Belt in the fifth round (147th overall) of the 2009 Major League Baseball draft after his junior year, and he signed for a signing bonus of $200,000. He started his professional career with the High-A Giants affiliate in San Jose, for whom he was a mid-season All Star. He worked with the Giants coaching staff and made an adjustment to his swing mechanics that helped him move quickly through the Giants farm system. He hit well at all three levels in 2010 finishing the year batting .352/.455/.620 with 23 home runs and 112 RBIs and gaining attention as one of the Giants top prospects.

In 2010, he played for the San Francisco Giants Class-AAA-affiliate Fresno Grizzlies, and was named a Baseball America Minor League All Star and an MiLB Organization All Star. He also played for the East Division Scottsdale Scorpions in the Arizona Fall League, where he was named a Rising Star and to the All Prospect Team. Belt played in the Arizona Fall League Rising Stars Game for the East team.

Belt married his high school sweetheart Haylee Stephenson on December 3, 2010, in their hometown of Lufkin, Texas. They have two sons, Greyson (born August 2014), and August (born July 2018).

After his strong showing in the minor leagues, Belt was invited to spring training in 2011, where he played in 28 exhibition games, the most on the team, and batted .282 with 3 home runs. On March 30, 2011, the Giants announced that Belt had been named to the opening day Major League roster, a moment captured in the series premiere of The Franchise. He started in his first major league game the next day and singled off of Los Angeles Dodgers pitcher Clayton Kershaw in his first major league at bat, finishing 1-for-3 with a walk. Belt hit his first major league home run on April 1, 2011, off Chad Billingsley. On April 20, Belt was optioned to Triple-A Fresno to make room on the roster for Cody Ross. He was hitting .192 in 17 games. Belt was recalled to the Giants on May 26 after injuries to Buster Posey and Darren Ford. On June 4, Belt was diagnosed with a hairline fracture, and was sent to the 15-day DL after being hit by a pitch in a game against the St. Louis Cardinals. On July 7, Belt was removed from the DL and optioned back to Fresno to continue his rehab assignment.

In August 2011, Belt was given the nickname “The Baby Giraffe” by Giants KNBR announcer Duane Kuiper, who commented that Belt looked like the animal while tracking down a fly ball in left field during a game against the Milwaukee Brewers. The nickname stuck and Belt became a fan favorite in San Francisco, with “Baby Giraffe” hats rivaling the number of “Panda” hats in the stands at AT&T Park in September 2011 (the panda hats are a reference to Giants star Pablo Sandoval, sometimes called “the Kung-Fu Panda”). Six Flags Discovery Kingdom named a real baby giraffe born in August after Belt.

In the 2012 NLCS, Belt hit .304 (7-for-23) in six games with a .565 slugging percentage. On October 28, 2012, Belt won his first World Series ring when the Giants swept the Detroit Tigers. Belt played a key part of the Giants’ clinching game in the World Series, starting the scoring by hitting a triple to right field in the second inning, scoring Hunter Pence from second.

Belt set new career highs in 2013, batting .289 with 17 home runs and 67 RBIs in 150 games, and he led the Giants with an .841 OPS. Belt got off to a slow start after losing 11 pounds to an opening-week stomach virus, but finished strong, batting .346 over the season’s final 51 games. Belt credited his improvement to changing his grip and moving back in the batter’s box. Belt was named National League Player of the Week for August 5–11 after collecting hits in all seven games played, while batting .440 (11-for-25) with five RBIs, 20 total bases, two home runs, and eight runs scored.

On February 1, 2014, Belt signed a one-year $2.9 million contract to avoid arbitration. On May 9, while batting at Dodger Stadium, Belt was hit on his left thumb by Dodgers pitcher Paul Maholm, suffering a broken thumb. Belt was activated from the disabled list on July 4, only to return to the disabled list on July 21 after suffering a concussion while fielding during batting practice. Belt was activated August 2, but was placed on the DL again August 8 when his concussion symptoms continued. Belt was reactivated from the disabled list on September 15.

In the 2014 postseason, Belt batted .295 (18-for-61) with 8 RBI and 11 walks in 17 games. In Game 2 of the 2014 NLDS versus the Washington Nationals, Belt hit a solo home run in the top of the 18th inning to break a 1–1 tie in the 18th inning after 6 hours and 23 minutes of game play, helping the Giants to an eventual 3–1 series win. On October 29, 2014, Belt won his second World Series ring when the Giants defeated the Kansas City Royals in seven games. Belt, along with teammate Hunter Pence, hit safely in all seven games of the series, the only players on either team to do so.

On February 3, 2015, Belt and the Giants avoided arbitration by agreeing to a one-year, $3.6 million contract. On May 17, Belt accomplished a rare feat when he collected 3 hits, including a home run, for 3 games in a row against the Cincinnati Reds. He was only the second Giants player to do so since 1900. Barry Bonds had a similar three-game streak in 2000. Belt recorded another unusual statistic since he hit the home runs on 3 consecutive days after not hitting any in his first 30 games. The last player to have done so was also Belt in the 2012 season when he hit home runs in 3 consecutive games after not hitting any in his first 48 games that season.

On February 10, 2016, Belt and the Giants agreed to a one-year, $6.2 million contract to avoid arbitration. On April 9, 2016, Belt and the Giants agreed to a 5-year, $72.8 million contact extension through 2021. After winning the 2016 National League All-Star Final Vote, Belt was selected to his first All Star Game.

In 2016, Belt led all Giants batters with 104 walks, 17 home runs, a .394 on-base percentage, and .868 OPS, and set a new career-high with 82 RBI. Belt became the first Giant to record 100 walks in a season since Barry Bonds in 2007. For the season, he had the lowest ground ball percentage of all major league hitters (26.3%).

In 2017, Belt tied his career-high with 18 home runs before suffering a season-ending concussion on August 4.

On April 22, Belt set a new MLB record for most pitches seen in a single at bat, with 21 against the Angels’ starting pitcher, Jaime Barria. Belt fouled off 16 pitches (15 with two strikes) against the right-hander in his first plate appearance of the game, in the top of the first inning. The at bat lasted 12 minutes and 45 seconds, and ended with a fly out to right fielder Kole Calhoun. Belt was also named the National League Player of the Week on May 21. On June 2, Belt underwent an appendectomy. In 2018 he batted .253/.342/.414 with 14 home runs and 46 RBIs.

In 2019 he batted .234/.339/.403 with 76 runs, 17 home runs, and 57 RBIs in 526 at bats. He had the lowest ground ball percentage in the National League (28.3%).