During pathogen attack, the host plant induces genes to ward off the pathogen while the pathogen often induces host genes that increase susceptibility to the pathogen. Gene expression studies identified many soybean genes altered in expression in resistant and susceptible plant roots over time during infection by soybean cyst nematode (Heterodera glycines; SCN). However, it is difficult to assess the role and impact of these genes on resistance and susceptibility by using gene expression patterns alone, because the nematode injects proteins into the host. These nematode effector proteins interfere with and subvert the normal molecular mechanisms of the host cell. Therefore, we cloned >110 soybean genes from gene expression experiments using microarrays and RNA-Seq deep sequencing. The genes were overexpressed in soybean roots of composite plants to determine their impact on SCN development. Several overexpressed genes decreased the number of mature SCN females more than 50% at 32-35 days after inoculation; numerous other genes increased the number of mature females by more than 150%. Genes that reduced the number of mature females per plant by more than 50% when overexpressed, included genes encoding a β-glucanase, two lipases, calmodulin, a possible transcription factor, as well as proteins of unknown function. Four genes increased the number of mature SCN females more than 200%, while eleven more genes increased the number of mature SCN females more than 150%. Genes enhancing susceptibility included several transporters, pectate lyase, a Ca-dependent kinase and ACC oxidase. Our data support a role for auxin and ethylene in susceptibility of soybean to SCN. These studies highlight the contrasting gene sets induced by host and nematode during infection and provide new insights into the interactions between host and pathogen at the molecular level. Some genes that conferred resistance to SCN were also tested against the root-knot nematode (RKN), Meloidogyne incognita. Many of the genes that conferred resistance to SCN also conferred resistance to RKN. This demonstrated that the genes conferred resistance across genera and provides new strategies for developing broad resistance in plants to parasitic nematodes.