The study was conducted to determine the effects of mineral methionine hydroxy analogue chelate (MMHAC) partially replacing inorganic trace minerals in sow diets on epigenetic and transcriptional changes in muscle and jejunum of progeny. The MMHAC is zinc (Zn), manganese (Mn), and copper (Cu) chelated with methionine hydroxy analogue (Zn-, Mn-, and Cu-MHAC). On d 35 of gestation, 60 pregnant sows were allotted to 2 dietary treatments in a randomized completed block design using parity as a block: (1) ITM: inorganic trace minerals with zinc sulfate (ZnSO4), manganese oxide (MnO), and copper sulfate (CuSO4) and (2) CTM: 50% of ITM was replaced with MMHAC (MINTREXtrace minerals, Novus International Inc., St Charles, MO). Gestation and lactation diets were formulated to meet or exceed NRC requirements. On d 1 and 18 of lactation, milk samples from 16 sows per treatment were collected to measure immunoglobulins (IgG, IgA, and IgM) and micromineral concentrations. Two pigs per litter were selected to collect blood to measure the concentration of immunoglobulins in the serum, and then euthanized to collect jejunal mucosa, jejunum tissues, and longissimus muscle to measure global DNA methylation, histone acetylation, cytokines, and jejunal histomorphology at birth and d 18 of lactation. Data were analyzed using Proc MIXED of SAS. Supplementation of MMHAC tended to decrease (P = 0.059) body weight (BW) loss of sows during lactation and tended to increase (P = 0.098) piglet BW on d 18 of lactation. Supplementation of MMHAC increased (P < 0.05) global histone acetylation and tended to decrease myogenic regulatory factor 4 (MRF4) messenger ribonucleic acid (mRNA) (P = 0.068) and delta 4-desaturase sphingolipid1 (DEGS1) mRNA (P = 0.086) in longissimus muscle of piglets at birth. Supplementation of MMHAC decreased (P < 0.05) nuclear factor kappa B (NF-κB) mRNA in the jejunum and DEGS1 mRNA in longissimus muscle, and tended to decrease mucin-2 (MUC2) mRNA (P = 0.057) and transforming growth factor beta 1 (TGF-β1) mRNA (P = 0.057) in the jejunum of piglets on d 18 of lactation. There were, however, no changes in the amounts of TNF-α, IL-8, TGF-β, MUC2, and MYF6 in the tissues by MMHAC. In conclusion, maternal supplementation of MMHAC could contribute to histone acetylation and programming in the fetus, which potentially regulates intestinal health and skeletal muscle development of piglets at birth and weaning, possibly leading to enhanced growth of their piglets. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.