Genetic knockout (KO) models are valuable tools for understanding biological functions and disease mechanisms. KO models in rats have fallen behind those in mice which limits advances in areas where rats have advantages because they can perform more complex cognitive tasks. Two widely used rat strains are Sprague Dawley (SD) and Long Evans (LE). Creating conditional KO models requires crossing Floxed and Cre lines with the constructs of interest but if they are on different genetic backgrounds, offspring will differ not only on the targeted gene but on genes of the differing background strains. We evaluated strain differences in SD and LE rats for behaviors that included: open-field locomotor activity in familiar and novel contexts, acoustic and tactile startle, egocentric and allocentric learning and memory, conditioned freezing, and working memory. Strain differences were found on open-field activity, startle prepulse inhibition, swimming, Cincinnati water maze (CWM), conditioned freezing, and 72 h home-cage activity. However, in the Morris water maze (MWM), performance was comparable between strains during acquisition and reversal, with LE rats performing slightly better in a third, shift phase with the platform in a third location. These data provide information on similarities and differences between SD and LE rats that may be useful to know when these strains are used to create conditional KO models or in regulatory safety studies.