Sequence-specific multivalent molecular recognition has been recognized to play a major role in biological processes. Furthermore, sequence-specific recognition motifs have been used in various artificial systems in the last years, e.g., to emulate biological processes or to build up new materials with highly specific recognition domains. In this article, we present the preparation of cyclodextrin (CD)-based strands and complementary and non-complementary strands modified with guest molecules and the investigation of their complexation behavior towards each other by isothermal titration calorimetry (ITC). As complementary binding motifs n-butyl and α-CD and adamantane and β-CD were selected. It was found that it is possible to realize sequence-specific molecular recognition by the use of host–guest chemistry, but the recognition motifs as well as the linkages have to be chosen very carefully. In the case of trivalent systems one adamantane moiety must be included to induce preferred formation of 1:1 adducts. Due to the too weak interaction between n-butyl and α-CD these systems have a negative chelate cooperativity and open adducts are preferentially formed. As soon as two adamantane moieties are present, the complementary systems have a positive chelate cooperativity and double-stranded structures are favored over open adducts. In this system the n-butyl moiety provides insufficient discrimination towards α- and β-CD and no sequence specificity is observed. By the combination of three adamantane moieties sequence specificity can be generated. Exclusively with the complementary CD sequence double-stranded structures are formed, with non-complementary strands aggregates of higher stoichiometry are generated.