Shading has been used to produce high-quality lettuce (Lactuca sativa) in locations where production conditions are not optimal for this cool-season crop. To learn what additional benefits shading provides if heat-tolerant cultivars are used and to understand the effects of shading on growth, sensory quality, chemical content, and transcriptome profile on heat-tolerant lettuce, we grew two romaine lettuce cultivars with and without shading using 50% black shadecloth in 2018 and 2019. Shading reduced plant leaf temperatures, lettuce head fresh weights, glucose and total sugars content, and sweetness, but not bitterness, whereas it increased lettuce chlorophyll b content compared with unshaded controls. Transcriptome analyses identified genes predominantly involved in chlorophyll biosynthesis, photosynthesis, and carbohydrate metabolism as upregulated in unshaded controls compared with shaded treatments. For the tested cultivars, which were bred to withstand high growing temperatures, it may be preferable to grow them under unshaded conditions to avoid increased infrastructure costs and obtain lettuce deemed sweeter than if shaded.