[3] Sean's older brother, Robert, was a catcher in the Nationals’ minor league system for five years (2002–06), and is the head coach/instructor at Total Baseball Academy in Clearwater, Florida.

[3][4] Rodriguez attended Miami Coral Park High School where he played center field for the baseball team.

He transferred after his sophomore year to G. Holmes Braddock High School, where Rodriguez played shortstop for the baseball team.

[7] Rodriguez, then primarily a shortstop, began his professional career for the Rookie League Tempe Angels in 2003.

[10] In 2006, he split the year between the Single-A Rancho Cucamonga Quakes with whom he batted .301/.377/.545 and was 2nd in the California League with 24 home runs, the Double-A Arkansas Travelers, and the Triple-A Salt Lake Bees (just one game for them).

His 135 games were a career high for him, and so were his .307/.387/.557 batting average, 29 home runs, 77 RBIs 522 at-bats, and 34 doubles.

On April 18, he was recalled from the Bees and made his major league debut against the Seattle Mariners the next day.

[3] On September 1, 2009, he was traded to the Tampa Bay Rays as the player to be named in a deal that sent Scott Kazmir to the Angels.

[10] Rodriguez's final 2009 stats between Salt Lake City and Durham included him batting .294/.397/.608 (3rd among all minor leaguers), with 30 home runs (tied for 7th among all minor leaguers, and first in the Angels organization) and 98 RBIs (first in the Angels organization) in 385 at-bats.

[21][22] On August 21, Rodriguez was optioned to Triple-A after the team activated Luke Scott from the disabled list.

[3] Despite hitting a career-low .211 in 237 at bats over 96 games for the Rays in 2014, Rodriguez had a career-high .443 slugging percentage and set career highs in home runs (12) and RBIs (41).

[27][28] Pirates minor league right handed pitcher Buddy Borden was the player to be named later, as he was sent to the Tampa Bay Rays to complete the trade for Rodriguez.

[3] On October 7, 2015, Rodriguez was ejected from the NL Wild Card game for his role in a benches-clearing brawl after Chicago Cubs pitcher Jake Arrieta was intentionally hit by a pitch from Pirates relief pitcher Tony Watson.

[35] On the afternoon of January 28, 2017, Rodriguez was injured near his Miami home when his Chevy Suburban SUV was struck in a side collision by a stolen police cruiser.

[37][38][39] In the collision Rodriguez's rotator cuff on his non-throwing left arm was severely torn, his labrum was damaged, and his biceps tendon was dislocated.

On April 24, Rodriguez was promoted to the major leagues after Jean Segura and Scott Kingery were injured.

In 2019 with the Triple–A Lehigh Valley IronPigs of the International League, Rodriguez slashed .267/.327/.622 with four home runs and 12 RBI in 45 at-bats.

On July 24, Rodriguez was selected to the 40-man roster, but hit the injured list shortly thereafter due to an unspecified medical reason.

[50] On March 11, 2022, Rodriguez was hired as a player development instructor for the Philadelphia Phillies, effectively ending his playing career.