Thompson, 5-0 at Triple-A Portland with a 3.79 ERA in seven starts, will take the rotation spot that opened up when Woody Williams went on the disabled list with a strained left calf May 13.
The right-hander was signed as a six-year free agent this off-season by the only club he has ever known.
Thompson came into the season with a 49-47 mark and a 4.57 ERA. His ERA has gone down each of the last three seasons from 4.42 to 3.15 last year. He was originally a fifth round pick by San Diego in 1999.
To make room for Thompson on the roster, the Padres optioned right-hander Cla Meredith to Portland.