Sosa, a designated hitter against the Texas Rangers, hit a 1-0 pitch from Kenny Rogers into the bullpen in left-center field.
It was only the 12th homer of the year for Sosa, who is batting just .235 and has been plagued by injuries. He had hit safely in eight straight games until an 0-for-3 performance Monday.
Sosa, 36, passed Mark McGwire on the all-time list July 18th with his 584th homer. In 1998, he and McGwire chased Roger Maris' single-season home run record of 61. Sosa finished with 66 while McGwire had 70. Barry Bonds hit 73 in 2001.
Willie Mays is fourth on the career homers list with 660.
Sosa was on the disabled list May 5-24 with an infection in the bottom of his left foot.