Payton attended Zanesville High School in Zanesville, Ohio, and starred in soccer, basketball, and baseball. He was also an excellent student and graduated 4th in his class. While in Zanesville Payton played for the Junior Pioneers. After his Senior year he helped lead the Midland Redskins of Cincinnati to the Connie Mack World Series Title where he was named MVP of the tournament. That exposure helped lead to a full ride scholarship to Georgia Tech where he would team up with future Major League All Stars Nomar Garciaparra and Jason Varitek to help lead Georgia Tech to their first ever World Series appearance in school history. The Yellow Jackets came up short losing to Oklahoma in the 1994 Championship game.
Selected by the Mets in the first round (29th pick) of the 1994 amateur draft, Payton hadn't fulfilled the great expectations he projected Georgia Tech when he was drafted in the first round with fellow All Americans and Teammates Nomar Garciaparra and Jason Varitek, due in large part to four surgeries while in the minor leagues. Payton had three elbow surgeries, two of which were Tommy John, and surgery on his left shoulder. He spent the better part of his first five years on and off the DL while rehabbing from surgeries. When asked about his unfortunate string of injuries during an interview, Jay responded simply "I just got unlucky. There is nothing you can do about it. All you can say is Cheese and Crackers Dave, Cheese and Crackers." He made his debut in 1998 after finally battling through all the elbow troubles. He helped lead the Mets to a World Series berth as the starting CF in 2000, his official rookie year, in which he finished third in the rookie of the year voting. With limited duty in 2001 due to a torn hamstring early in the season, the Mets finally gave up on him and he was traded to the Rockies during the 2002 season.
In 2003, Payton enjoyed his most productive season with career highs in home runs (28), RBI (89), runs (93), hits (181), doubles (32), on base percentage (.354), slugging average (.512), at bats (600) and games played (157), and added a respectable .302 batting average. He was signed by San Diego as a free agent at the end of the season. But Payton had a subpar 2004 season batting .260 with eight homers and 55 RBI in 143 games. In December, he was sent to Boston for Dave Roberts and took over Roberts' role as the team's fourth outfielder.
Payton was designated for assignment by the Red Sox on July 7, 2005, after being publicly disgruntled over his lack of playing time. On July 13, he was traded to the Oakland Athletics for pitcher Chad Bradford. Payton hit a home run on the first pitch in his first at bat for his new club, and earned a cult status for a brief period after winning many games for the A's with an otherwise struggling offense. In 2006, Payton played regularly in the outfield for the Athletics while batting .296 with 10 home runs and 59 RBIs. On July 3, 2006, he hit his 100th career home run. On December 8, Payton agreed to terms on a two-year, $9.75 million contract with the Baltimore Orioles. In March 2009, Payton suffered a shoulder injury while lifting weights.
On January 20, 2010, Payton signed a minor league contract with his former team the Colorado Rockies. Payton was called up to the Colorado Rockies active roster in September after spending most of the season with the Rockies minor league affiliate the Colorado Springs Sky Sox. He hit .343 with the Rockies in 35 AB. He retired in February 2011.