The Padres announced the move Sunday. Left-hander Travis Wood was designated for assignment.
The 27-year-old Lyles joined San Diego in early August, soon after being released by Colorado. He was a combined 1-5 with a 7.75 ERA in 38 games, including five starts.
Lyles is 28-48 with a 5.43 ERA in seven seasons with Houston, the Rockies and the Padres.
Wood was 4-7 with a 6.80 ERA in 39 games for Kansas City and San Diego last season. The 30-year-old lefty pitched 11 times for the Padres, all of them starts.