Decoding the mechanisms of plant defense against plant pathogens in a scenario where antagonistic activity and the plant growth-promoting effects of useful organisms intervene simultaneously is a new frontier of plant pathology. Here, we demonstrated that (i) two selected strains of
Trichoderma asperellum
and
Trichoderma atroviride
promoted tomato (
Solanum lycopersicum
) growth and reduced the severity of disease caused by the oomycete
Phytophthora nicotianae
and (ii) the genetic patterns of the components of the experimental model system tomato–
Trichoderma
spp.–
P. nicotianae
were differentially expressed. The beneficial effects in both the promotion of the growth of host plant and the biological control of the pathogen by two selected strains of different
Trichoderma
species were tested both
in planta
and
in vitro
. In both respects,
T. atroviride
demonstrated to be more effective than
T. asperellum
. Additionally, the simultaneous transcriptional reprogramming of several plant defense-related genes, pathogen effectors, and mycoparasitism-related genes in tomato,
P. nicotianae
, and
Trichoderma
spp., respectively, was evaluated during the three-component interaction. Results support the hypothesis that
Trichoderma
spp. elicit the expression of plant defense-related genes. As expected, a mycoparasitism-related gene was significantly up-regulated in
Trichoderma
-colonizing tomato plants infected by
P. nicotianae
. Finally, a marked up-regulation of the genes encoding two necrosis-inducing effectors was observed in
P. nicotianae
infecting tomato plants colonized by
Trichoderma
. In conclusion, this study is a contribution toward understanding the genetic pathways related with the ability of
Trichoderma
spp. to counteract the challenge of
P. nicotianae
infections on tomato. Additionally, the experiments revealed the beneficial effects in the tomato growth promotion of a new
T. atroviride
strain and its good antagonistic effectiveness in the biological control of root and crown rot incited by
P. nicotianae
, confirming that
Trichoderma
spp. can be a powerful tool in integrated pest management strategies of
Phytophthora
diseases of horticultural crops.