On July 3, in a home game against the Cubs, Flores became only the second Mets player to collect six hits in a game, the first being fellow Venezuelan infielder Edgardo Alfonzo, who did so in August 1999. In doing so, he raised his batting average 31 points from .224 to .255. He became the first player in Major League Baseball to accomplish the feat since C.J. Cron the day earlier and the first player in the National League to do so since Charlie Blackmon on April 4, 2014.

Flores signed as an international free agent from Venezuela with the New York Mets on August 6, 2007, his 16th birthday. He was rated in the Top 100 prospects by Baseball America prior to the 2009 (#47), 2010 (#88), and 2011 (#59) seasons.

In 2011, the Mets sent Flores back to the St. Lucie Mets of the Class A-Advanced Florida State League (FSL) to convert him from a shortstop into a third baseman. In 2012, Flores was selected at third base for the FSL All-Star Game. He went 3-for-4 with a run scored and three runs batted in, earning Most Valuable Player honors. He also appeared in the All-Star Futures Game for the second time in his career. The Mets promoted Flores to the Binghamton Mets of the Class AA Eastern League during the 2012 season. He finished the 2012 season with Binghamton batting .311/.361/.494 in 66 games with 8 home runs, 33 RBIs, and 20 walks.

Flores made the Mets’ roster for Opening Day in 2015. During the first week of the season, Flores struggled offensively and defensively as he made three errors and batted .158 in seven games. In nine games after the opening week, Flores batted .364 with three home runs. Soon thereafter, Flores was tied for third in all of baseball in errors committed with six. On May 16, Flores became the first National League position player to hit a grand slam batting ninth in a National League ballpark. The home run came off Milwaukee Brewers pitcher Matt Garza at Citi Field. The home run was his second career grand slam. On May 26, Flores at the time was tied for most home runs hit by a shortstop with Jhonny Peralta of the St. Louis Cardinals with seven. That same day, Flores hit his first career walk-off, a single, off Phillies’ pitcher Elvis Araújo in the bottom of the tenth inning with two outs scoring Juan Lagares for his second RBI of the game.

On April 15, 2018, Flores hit a walk-off home run to give the Mets a win against the Brewers. This was his third career walk-off home run. On June 26, Flores drove in the winning run against the Pittsburgh Pirates in the bottom of the 10th inning, giving the Mets a 4–3 victory. Earlier in the game, he had driven in the Mets’ first two runs as well. Flores’s game winner was his 9th walk-off RBI of his young career. He tied David Wright for the most walk-off RBIs in Mets’ history. On July 9, in the first game of a doubleheader against the Philadelphia Phillies, Flores hit a pinch-hit walk-off home run, breaking Wright’s record for the most walk-off RBI of any player in Mets franchise history. In 2018 he batted .267/.319/.417.

On January 21, 2019, Flores signed a one-year, $4.25 million contract with the Arizona Diamondbacks. He played in 89 games for the Diamondbacks in 2019, hitting .317/.361/.487 with 9 home runs and 37 RBIs in 265 at bats.

On February 4, 2020, Flores signed a two-year, $6 million contract including a third-year option with the San Francisco Giants.