Latos committed to attend the University of Oklahoma to play college baseball for the Oklahoma Sooners baseball team. However, many scouts expected Latos to be a first-round pick in the 2006 Major League Baseball (MLB) Draft. SchoolSports.com ranked Latos the fifth-best high school pitcher available in the 2006 Major League Baseball draft. The San Diego Padres selected Latos in the 11th round (333rd overall). He fell in the draft since his personality made him difficult to handle in high school, as he was considered immature, often yelled at teammates who made errors and reacted poorly when the umpire made a call with which he disagreed.

After the draft, Latos demanded a $3 million signing bonus from the Padres. When the Padres did not meet his demands, Latos enrolled at Broward College, a junior college, to pitch for their baseball team. As the Padres retained the right to sign Latos until the start of the 2007 MLB draft, they sent scout Joe Bochy to observe every start Latos made. Latos had a 10–3 win–loss record and a 2.03 ERA. Feeling that Latos was worth the gamble, the Padres paid Latos $1.25 million a few days before he would have re-entered the draft in 2007.

Latos started his professional career in 2007, minor league baseball with the Eugene Emeralds, the Padres’ Class A-Short Season affiliate in the Northwest League. Pitching in 16 games for Eugene, Latos had a 1–4 record and a 3.83 ERA. In 2008, Latos started the season with the Fort Wayne Wizards of the Class A Midwest League, but missed playing time during the season due to abdominal and shoulder injuries.

The Padres invited Latos to spring training in 2009, but he suffered a minor ankle sprain that limited his appearances. Latos started the 2009 season in Fort Wayne and allowed only one run in four starts. He was then promoted to the San Antonio Missions of the Class AA Texas League. At San Antonio, Latos had a 5–1 win–loss record and threw five perfect innings in his last start for San Antonio on July 9. Between Fort Wayne and San Antonio, Latos had an 8–1 record, a 1.38 ERA, 73 strikeouts, and a .168 batting average against (BAA). The Padres named Latos their Padres Minor League Pitcher of the Month for May. Latos was selected to play in the 2009 All-Star Futures Game, and threw one scoreless inning.

The Padres promoted Latos to make his major league debut on July 19, 2009, against the Colorado Rockies. In his major league debut, Latos pitched four innings, allowing three hits and two runs while striking out four, while throwing 75 pitches. He recorded his first major league win on July 24. Latos became the first pitcher in Padres history to win four of his first five career starts. Latos made ten starts for the Padres in 2009, pitching to a 4–5 record and a 4.68 ERA.

However, Latos lost his last five starts of the 2010 season, culminating with a 3–0 loss to the San Francisco Giants on October 3 that, combined with an Atlanta Braves win, eliminated the Padres from playoff contention. The San Diego Union-Tribune attributed his struggles at the end of the year to fatigue, as his 189 ⁄3 innings for the season were 66 ⁄3 more than he pitched in 2009.

On May 13, 2010, Latos threw a complete game shutout against the division foe San Francisco Giants. The only hit he allowed was an infield single. The Padres won the game 1–0. After posting a 5.47 ERA through May 1, Latos lowered his ERA down to 2.45 right before the All Star Break, also leading the league in BAA and WHIP (.193 and 0.97 respectively). On September 7, 2010, Latos set a major league record with a seven–inning, 10–strikeout performance in a win against the Dodgers. The victory was Latos’ 15th consecutive start logging at least five innings and allowing two or fewer earned runs, which was at the time the longest streak in modern baseball history (since 1900) according to the Elias Sports Bureau. The record would be broken by Félix Hernández, who recorded 17 such straight outings during the 2014 season. Previously the mark had been set by Greg Maddux (1993–94) and Mike Scott (1986), who had such streaks lasting 14 starts. On the season, Latos pitched to a 14–10 win–loss record in 31 games started, with a 2.92 (ERA), 1.08 walks plus hits per inning pitched (WHIP), and 189 strikeouts in 184 ⁄3 innings pitched. He placed eighth in voting for the National League Cy Young Award.

Latos started 2011 on the disabled list due to a spring training shoulder injury. He lost his first four starts of the season, extending his losing streak to nine consecutive starts dating back to 2010. The streak tied the longest streak in Padres history, held by Andy Benes and Dennis Rasmussen. Latos had a no-decision in his next start after the bullpen blew a save opportunity, preventing him from earning a win. He lost another decision for a 10-game losing streak that was one less than the club record held by Gary Ross. Latos won on May 15 against the Colorado Rockies to end his losing streak. He ended the 2011 season with a 9–14 record and a 3.47 ERA.

After the 2011 season, the Cincinnati Reds were looking for another frontline starter to pair with Johnny Cueto in their starting rotation. On December 17, 2011, the Padres traded Latos to the Reds in exchange for prospects Yonder Alonso, Yasmani Grandal, and Brad Boxberger, along with veteran starting pitcher Edinson Vólquez.

In the last week of June 2012, Latos pitched two complete games. He was named the National League Player of the Week for the week ending July 1. Latos finished the 2012 season with a 14–4 win–loss record a 3.48 ERA. The Reds reached the playoffs, and faced the San Francisco Giants in the 2012 National League Division Series (NLDS). On October 11, 2012, Latos gave up a grand slam to Buster Posey in a 6-run top of the fifth inning in the elimination game of the NLDS. Latos took the loss in this game, as the Reds were eliminated.

Mat and his wife, Dallas, met through her then-roommate, who was dating Mat’s friend, a minor league baseball player. Mat and Dallas participated in the NOH8 Campaign in 2013. The couple own a cat, named Cat Latos. They purchased a home in Indian Hill, Ohio, in 2013. They had their first child, a son named Landon, in August 2014. Mat and Dallas divorced in 2017.

Latos had surgery to remove bone chips from his elbow during the offseason. During spring training in 2014, Latos tore cartilage in his left knee, which was repaired with surgery. His knee had not fully recovered in time for Opening Day of the 2014 season, which he started on the disabled list. He began a rehabilitation assignment with the Louisville Bats of the Class AAA International League on May 26, and made his 2014 season debut with the Reds on June 14. Latos said that he came back at “80–90 percent” effectiveness due to his desire to help his team, but experienced setbacks with his knee during the season. He averaged 90.7 miles per hour (146.0 km/h) on his fastball, down from 92.5 miles per hour (148.9 km/h) during the 2013 season. His last start came on September 7, as he suffered a bone bruise on the elbow of his pitching arm. His 2014 season ended with a 5–5 record and a 3.25 ERA in 16 starts.

On July 30, 2015, in a three-team trade, the Los Angeles Dodgers acquired Latos, Michael Morse, Bronson Arroyo, Alex Wood, Jim Johnson, Luis Avilán, and José Peraza, while the Marlins acquired minor league pitchers Victor Araujo, Jake Brigham, and Kevin Guzman, while the Atlanta Braves received Héctor Olivera, Paco Rodriguez, minor league pitcher Zachary Bird, and a competitive balance draft pick for the 2016 MLB draft. He pitched to a 6.66 ERA in 24 ⁄3 innings. He lost his starting job due to his poor performance and was designated for assignment on September 17. The Dodgers released Latos on September 25.

On September 28, 2015, Latos signed a contract with the Los Angeles Angels of Anaheim that would allow him to pitch the last week of the season for them. Latos was not eligible to pitch for the Angels in the postseason. He made his first appearance for the Angels as a relief pitcher on September 29. Latos had a 4.91 ERA in 3 ⁄3 innings pitched for the Angels.

Latos signed a minor league contract with the Washington Nationals on June 29. After making three appearances for the Gulf Coast Nationals of the Rookie-level Gulf Coast League, the Nationals assigned Latos to the Syracuse Chiefs of the International League. He made his Nationals debut on September 4, 2016, against the Mets. He pitched 9 ⁄3 innings for the Nationals, recording a 6.52 ERA.

On February 16, 2017, Latos signed a minor league contract with the Toronto Blue Jays. After not winning a spot on the Blue Jays’ roster in spring training, Latos accepted an assignment to the Buffalo Bisons of the International League. He made two starts for the Bisons, pitching to a 1.00 ERA in nine innings, and the Blue Jays promoted Latos to the major leagues on April 21 after injuries to the team’s starting rotation. Latos started three games for the Blue Jays, pitching to a 6.60 ERA and 1.80 WHIP. The Blue Jays designated Latos for assignment on May 5, and outrighted him back to Buffalo on May 8. He was released by the team on May 30.

On April 10, 2018, Latos signed with the New Jersey Jackals of the independent Can-Am League. During a game on June 9, Latos threw at a batter after another player collided with his catcher. The batter charged the mound, and a brawl ensued, leading to Latos’s ejection.

Following the conclusion of the season, Latos was released by the Jackals on October 3, 2018.

On March 28, 2019, Latos signed with the Southern Maryland Blue Crabs of the Atlantic League of Professional Baseball. He became a free agent following the season.

On January 29, 2020, Latos signed with the New Jersey Jackals of the Frontier League.