Five cultivars and two populations of wild-type seedlings of American elm (Ulmus americana), 3 and 4 years old, were examined for differences in their abilities to compartmentalize and resist infection by artificially inoculating with Ophiostoma novo-ulmi. Morphological characteristics of tree defence, often referred to as the compartmentalization of decay in trees model, were used as a conceptual framework, with particular emphasis on the limiting of tangential spread of infection within the xylem and barriers that limit spread outwards to cells formed after infection. To investigate the change in functional xylem over time, 3-year-old trees were assessed at multiple time points following inoculation for hydraulic conductivity. Three and four-year-old cut trees were placed in 0.1% w/v safranin O for 18 to 24 hr to indicate functional xylem. Transverse sections of the stained stems were used to calculate per cent of sap-conducting xylem area and the per cent of circumference conducting of first formed cells and later formed cells. At each collection time, trees were assessed for disease severity on a 1–12 scale, based on the percentage of permanent wilt in the crown. There was considerable variation between cultivars in disease severity and their capacity to localize and resist infection. “Prairie Expedition,” which had the lowest disease severity rating in 2015 and the second lowest in 2016, consistently limited the spread of infection into newly formed xylem and had functional xylem around the entire circumference of the stem at 90 days post-inoculation. “Valley Forge” in 2016 had the lowest overall disease severity rating and was the only cultivar to consistently limit the tangential spread of infection within extant xylem. This research identifies key characteristics that some cultivars have to resist and limit infection and provides new information that can be used in disease screening programmes to evaluate other cultivars and older plant material.