Cultivated lettuce is more sensitive to salinity stress than its wild progenitor species potentially due to differences in root architecture and/or differential uptake and accumulation of sodium. We have identified quantitative trait locis (QTLs) associated with salt-induced changes in root system architecture (RSA) and ion accumulation using a recombinant inbred line population derived from a cross between cultivated lettuce (Lactuca sativa ‘Salinas’) and wild lettuce (L. serriola). Components of RSA were quantified by replicated measurements of seedling growth on vertical agar plates containing different concentrations of NaCl in a controlled growth chamber environment. Accumulation of sodium and potassium ions was measured in replicates of greenhouse-grown plants watered with 100 mM NaCl water. A total of 14 QTLs were identified using multi-trait linkage analysis, including three major QTLs associated with general root development, root growth in salt stress condition, and ion accumulation. The three major QTLs, qRC9.1, qRS2.1, and qLS7.2, were linked with markers E35/M59-F-425, LE9050, and LE1053, respectively. This study provides regions of lettuce genome contributing to salt-induced changes in RSA and ion accumulation. Future fine-mapping of major QTLs will identify candidate genes underlying salt stress tolerance in cultivated lettuce.