On October 2, in the first postseason game for both Longoria and Tampa Bay, Longoria hit two home runs in his first two at-bats to help lead the Rays past the Chicago White Sox 6–4. Longoria is the first rookie and second player overall to homer in his first two postseason at bats. The first to do so was Longoria’s hitting coach at Triple-A Durham, Gary Gaetti, who had his historic effort with the Minnesota Twins in 1987.

The similarity of his name with actress Eva Longoria’s has brought about playful comparisons between the two. Although both are Americans of Mexican descent, they are not related. When asked as a college baseball player in 2005 about the name similarity, he admitted that he got “ragged on it a lot, but I don’t mind. My friends and I think she’s hot.” However, when asked about it again in 2008, Evan said that he was “done talking about that. I did it all through the minor leagues. That’s all I had to hear was her name associated with mine. I think we’re kind of past that. That’s all.” After he was named to the 2008 Major League Baseball All-Star Game, Eva sent Evan a bottle of champagne and a note thanking him for “doing the Longoria name proud”. In return, Evan sent Eva three signed jerseys. The name similarity between Evan and Eva has led to some heckling by opposing fans against him.

Following a successful MVP summer in 2006 in the Cape Cod League with the Chatham A’s where he played second base, Longoria shared the Big West Conference Player of the Year honors (with Justin Turner) during his junior year at Long Beach State. When he first started attending Long Beach State University, he majored in kinesiology. However, he switched to the department of Criminal Justice because it was somewhat less time-consuming and, therefore, would not interfere with the baseball schedule as much.

Longoria was selected by the Tampa Bay Rays as the third overall pick in the 2006 Major League Baseball draft. Longoria was called the “best pure hitter” among college players in the 2006 draft class by Baseball America. He was the highest draft selection in school history. Tampa Bay gave him a $3 million signing bonus.

After signing with the Rays, Longoria tore through his first assignments in the minor leagues. In 2006, after just eight games with the short season Single-A Hudson Valley Renegades, Longoria was promoted to the Visalia Oaks and impressed the organization with his quick success, hitting .327/.402/.618 with eight home runs and 28 RBIs in 28 games. This earned him a promotion to the Double-A Montgomery Biscuits, where he hit .267/.266/.486 with six home runs through the end of the season, and hit .345 in the postseason, including a walk-off two run home run in the Southern League Division Playoffs to put Montgomery into the championship. He was the 2007 Most Valuable Player with the Biscuits as well as a postseason all-star. On top of that he won a player of the week award. He was widely considered the top third base prospect in the minors and one of the top prospects at any position.

Longoria followed up his successful debut with another stellar year in 2007. Starting the year with Montgomery, Longoria hit .307/.403/.528 with 21 home runs and 76s RBI in 105 games for the Biscuits before a late-season promotion to the Triple-A Durham Bulls. In 31 games with the Bulls, he hit .269/.398/.490 with 5 home runs and 19 RBIs, but also had 29 strikeouts. He finished 2007 with a combined average of .299/.402/.520, 26 home runs, 95 RBIs, 110 strikeouts, and 73 walks for an OBP of .402.

In October 2007, sportswriter Ken Rosenthal opined that Longoria “might be next season’s Ryan Braun, making a rapid ascent to the majors.” Some scouts in particular said that the way that the ball “explodes off his bat” reminded them of Braun. He was expected to start at third for Tampa Bay in 2008 with the move of Akinori Iwamura to second base, but ultimately failed to make the opening day roster and was optioned to Triple-A Durham. According to reports, the Rays elected to send him down to complete his development, citing his short 31-game stint in Durham and drawing comparisons to the seasons of two other highly heralded third-base prospects.

On April 12, 2008, the Rays placed Willy Aybar on the disabled list and called up Longoria from Triple-A Durham to replace him on the major league roster and on the 40-man roster. Longoria made his major league debut that night going 1 for 3 with an RBI.

Longoria hit his first career home run on April 14, against the New York Yankees at Tropicana Field. He had his first career two-homer game on May 24, and drove in six runs as the Rays defeated the Baltimore Orioles 11–4. Both of the homers came off the Orioles’ Steve Trachsel, also a Long Beach State alumnus. On July 19, 2008, Longoria hit his first career grand slam off Toronto’s Roy Halladay in the fifth inning as part of a 6–4 winning effort.

On October 14, 2008, Longoria set the rookie mark for most home runs (4) hit in a postseason series, breaking Miguel Cabrera’s record set in 2003. The Rays made it to the 2008 World Series (their first in franchise history) but were defeated by the Philadelphia Phillies.

After the 2008 season, Longoria was honored with Sporting News Rookie of the Year Award for the American League, as well as the American League Rookie of the Year Award. He became the fourth third baseman to win the award. He also became the sixth player and the first since Nomar Garciaparra in 1997 to win a Rookie of the Year Award unanimously. He was also named the third baseman on the Topps Rookie All-Star Team.

In April, Longoria knocked in his 100th career RBI, in his 135th game. The only then-active players to get to 100 RBIs more quickly were Ryan Braun (118 games) and Albert Pujols (131 games). At the end of April, Longoria became the first player in Rays franchise history to be named the AL Player of the Month. He had also won two of the four Player of the Week awards for the month of April. Longoria drove in 131 runs in his first 162 games in the majors, the third-highest total through May 2009 of any active player. Longoria was selected by the fans to start the 2009 MLB All Star Game on July 5, 2009. Due to a finger injury, he was kept out of the lineup.

Entering August 1, Longoria was hitting .328 with a .919 OPS after the All Star Break. That night, he would continue his hot streak, becoming just the second Tampa Bay Ray to hit for the cycle, the first having been B. J. Upton in 2009. Longoria homered in the first, tripled in the third, singled in the seventh, and doubled in the ninth. In the ninth, Longoria was originally called out at second before replay overturned the call. Per Elias Sports Bureau, Longoria became the first player to hit for the cycle while having one of his hits reviewed. Offensively, Longoria had a down year, slashing .261/.313/.414 with 20 home runs, however he excelled defensively, and won his third career Gold Glove Award

Longoria was called upon on March 19, 2009, to replace Chipper Jones in the World Baseball Classic.

In 2010, Longoria hit for the highest average of his career at .294 and was selected to play in the All Star Game for the third consecutive season. He performed well, getting a hit in his only official at-bat, in addition to having a walk and a run scored. Across the board, Longoria’s 2010 season was statistically impressive, including 96 runs scored and 46 doubles as well as 5 triples. Surprisingly, though, his home run and RBI production fell from 33-113 in 2009 to 22-104 in 2010. After the season, Longoria won the Gold Glove Award at third base for the second straight year.

Longoria was named the cover athlete for Major League Baseball 2K10, succeeding Tim Lincecum. Longoria also appears in a commercial for the game that advertises the $1 million prize given to the first person to pitch a perfect game in MLB 2K10. In the commercial, Longoria breaks up a perfect game with a home run. On August 8, 2010, Longoria broke up a no-hitter in the ninth inning with two outs. Longoria spoiled Brandon Morrow’s attempt with a putt-shot to the Blue Jays’ second baseman, who was unable to make a play on it. Brandon Morrow was left with a 17-strikeout one-hitter (which would have tied Nolan Ryan for most strikeouts in a no-hitter).

On September 28, 2011, Longoria hit a walk-off home run in extra innings against the New York Yankees to give the Rays an 8-7 victory, and more importantly, a spot in the playoffs. Earlier in the month, the Rays were facing a deficit of nine games in the wild card race to the Boston Red Sox. However, an epic collapse of the Red Sox, where they went 7-20 in the final games of the year, and a surge of the Rays, allowed them to overtake the Red Sox and eliminate them on the final day of the regular season. Longoria’s home run came just three minutes after the Red Sox suffered a walk-off loss to the Baltimore Orioles.

Some of his 2013 highlights included playing in the most games of his career with 160; he missed two with a foot injury. He had a walk-off home run vs. the San Diego Padres on May 11 when the Rays were down, 6–7. It was his first walk-off home run since the Game 162 walk-off against the New York Yankees in 2011.

On March 8, 2011, his classic 1967 black and white Camaro RS, valued at $75,000, and a Buick GSX, valued at $25,000, were reported stolen from an Arizona lot. Longoria lives in California, but was having work done on the cars in Arizona.

On March 28, 2011, Longoria, David Price and Reid Brignac’s rental property in Port Charlotte, Florida, was broken into, while they were away at the nearby Charlotte Sports Park stadium for a game. According to the St. Petersburg Times, police estimated $56,000 in lost property from the burglary. Among the loot was Longoria’s AK-47 rifle.

A video showing Longoria being interviewed during batting practice when a foul ball flies in the direction of the reporter and is intercepted bare handed by the baseball player was published on YouTube on 6th May 2011. As of 16th May, the video already had 1.2 million views. As of July 2020, the video had more than 10 million views.

On April 30, 2012, Longoria suffered a partially torn hamstring after sliding to second base when being caught stealing. His injury placed him on the 60-day disabled list as Longoria was expected to miss from 6–8 weeks. He missed 13 weeks and returned to the lineup on August 7, 2012. In the 85 games Longoria missed, the Rays earned a record of 41-44. The rest of the season, the Rays were 49-28, for a 63.6% winning percentage.

On October 3, 2012, Longoria finished off the 2012 season with three home runs in the final game.

On November 26, 2012, Longoria was signed to a 6-year, $100 million contract extension that could keep him in Tampa Bay through 2023.

In February 2012, Longoria confirmed he was dating January 2010 Playmate of the Month Jaime Edmondson, who was also a contestant on the 14th season and the 18th season of The Amazing Race. Longoria and Edmondson married on December 31, 2015. They have two children.

On August 19, 2013, Longoria hit his 1st home run of the season, giving him his fourth 25-homer season, which tied him with Carlos Peña for the most such seasons in Tampa Bay history.

Longoria drove in his 500th career RBI after hitting a sacrifice fly vs. the New York Yankees on June 20, 2013, to plate Sean Rodriguez.

Longoria hit two home runs on September 25, 2013, vs. the New York Yankees at Yankee Stadium. These home runs gave him No. 30 and No. 31 on the year, also giving him his third career 30 HR season. The Rays won the game 8–3.

During the 2013 American League Wild Card tie-breaker game vs. the Texas Rangers, Longoria hit a two-run home run in the third inning. It would eventually be the go-ahead run, giving the Rays a fourth playoff berth in franchise history.

Longoria owns a restaurant in South Tampa called “Ducky’s” which opened in December 2013.

The 2014 season was Longoria’s 7th season as a Major League player.

On Opening Day, Longoria went 0-4, but quickly got on pace and on April 4, 2014, Longoria hit the 163rd home run of his career to tie the Rays franchise record of most home runs, a record which was held for many years by Carlos Peña.

Longoria came out of the gate swinging, belting 19 first half home runs with a .526 slugging percentage. His first half performance earned him a spot in the 2016 All-Star Final Vote. In the end, the three time All-Star would lose out to Michael Saunders of the Toronto Blue Jays.

On December 20, 2017, the Rays traded Longoria and cash considerations to the San Francisco Giants for Christian Arroyo, Denard Span, Matt Krook, and Stephen Woods.

On May 5, 2018, Longoria hit a double to mark his 1,500th career hit in an 11-2 victory over the Atlanta Braves. On June 14, Longoria was hit by a pitch on his left hand and left the game. Soon after, it was revealed that there was a fractured fifth metacarpal in his left hand. Two days into his injury, it was revealed that Longoria was facing surgery, which would likely keep him out for 6–8 weeks. Longoria experienced a disappointing 2018 season with the Giants as he hit a career-low 16 home runs (which led the Giants), had a career low in runs batted in with 54 and tied his career low with a .244 batting average.

In 2019 he batted .254/.325/.437, with 20 home runs and 69 RBIs in 453 at bats.

On August 21, 2020, Longoria reached 300 MLB career home runs.